Pulmonary Health Hub

Can allergen-specific immunotherapy cut the risk of asthma development in children with allergic rhinitis? Dr. Linda Cox discusses the potential implications of an ongoing retrospective review of Florida Medicaid records to determine if immunotherapy reduced asthma risk and its associated costs.

Can allergen-specific immunotherapy cut the risk of asthma development in children with allergic rhinitis? Dr. Linda Cox discusses the potential implications of an ongoing retrospective review of Florida Medicaid records to determine if immunotherapy reduced asthma risk and its associated costs.

Can allergen-specific immunotherapy cut the risk of asthma development in children with allergic rhinitis? Dr. Linda Cox discusses the potential implications of an ongoing retrospective review of Florida Medicaid records to determine if immunotherapy reduced asthma risk and its associated costs.

ORLANDO – Elevated levels of soluble CD14 in umbilical cord blood appear to be highly predictive of wheeze and cough in the first year of an infant’s life, Taiwanese investigators reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Children with elevated cord-blood soluble CD14 (sCD14) had nearly an eightfold risk for wheezing and a sixfold risk for cough in the first year, compared with children with low levels, said Dr. Yu-Lin Huang from the department of pediatrics at the Chang Gung Memorial Hospital and Chang Gung University in Keelung, Taiwan.

The finding lends credence to the hypothesis that prenatal factors play a role in the pathogenesis of asthma.

Soluble CD14 is a pathogen pattern receptor molecule that works with other receptors to recognize bacterial lipopolysaccharides (LPS) and mediate LPS-induced inflammation. Evidence for its utility as a biomarker for allergy and asthma has been decidedly mixed, however, said Dr. Huang.

One study, for example, showed that lower sCD14 levels at birth were associated with increased risk of wheeze at age 1 (Am. J. Respir. Crit. Care Med. 2004;169:70-6), whereas a different study showed that sCD14 levels are higher during acute asthma episodes (Am. J. Respir. Care Crit. Med. 2006;173:617-22).

Because allergic diseases have been steadily rising in Taiwan since the 1970s, the investigators hoped to clarify whether sCD14 level at birth and/or the urine leukotriene E4 to creatinine (LC) ratio at 1 month could be useful predictors of an individual child’s risk for future atopic diseases and asthma.

They recruited newborns delivered at the Chang Chung Memorial Hospital from October 2007 through September 2009, recording sCD14 levels at birth and collecting questionnaires from the mothers asking about parental medical and allergic histories. The questionnaires were repeated at 1, 6, 12, and 18 months.

At 1 month they collected and examined urine for the LC ratio, and followed with child blood and urine samples at 6 and 12 months, and mother’s blood sample at 6 months.

They defined outcomes at age 1 as parental report of wheezing, cough persisting for more than 3 weeks, rhinitis (runny or blocked nose in the absence of a cold or flu), rhinoconjunctivitis, rash (intermittent for at least 3 months), and atopy (positive specific immunoglobulin E to Dermatophagoides pteronyssinus, D.farinae, egg white, milk, Cladosporium herbarum, and wheat).

Of the 206 children available for follow-up at 1 year, wheeze was prevalent in 14%), and sCD14 levels in these children were significantly higher than in the 177 children with no reported wheeze (583 plus or minus 127 vs. 491 plus or minus 162 ng/mL, P = .001).

Similarly, prolonged cough was reported in 7% at 1 year, and these children also had significantly higher sCD14 levels in cord blood (615 plus or minus 170 vs. 496 plus or minus 157, P = .008).

There were no other significant associations with sCD14 and other outcomes. LC ratio at 1 month was not significantly associated with any of the outcomes.

In multiple logistic regression analysis, they found that factors significantly predictive for wheeze at 1 year included sCD14 (P = .002), duration of day care attendance (P = .005), and parental smoking, with each pack per day of cigarettes associated with a doubling of risk (P = .016).

Significant risk factors for prolonged cough include sCD14 (P = .008) and number of older siblings (P = .015).

In a comparison of high vs. low sCD14, the adjusted odds ratio for wheeze with high levels was 7.74 (P less than .001). The adjusted OR for prolonged cough was 5.99 (P = .021).

The study was supported by a Chang Gung Research project grant. Dr. Huang reported that he had no relevant disclosures.

ORLANDO – Elevated levels of soluble CD14 in umbilical cord blood appear to be highly predictive of wheeze and cough in the first year of an infant’s life, Taiwanese investigators reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Children with elevated cord-blood soluble CD14 (sCD14) had nearly an eightfold risk for wheezing and a sixfold risk for cough in the first year, compared with children with low levels, said Dr. Yu-Lin Huang from the department of pediatrics at the Chang Gung Memorial Hospital and Chang Gung University in Keelung, Taiwan.

The finding lends credence to the hypothesis that prenatal factors play a role in the pathogenesis of asthma.

Soluble CD14 is a pathogen pattern receptor molecule that works with other receptors to recognize bacterial lipopolysaccharides (LPS) and mediate LPS-induced inflammation. Evidence for its utility as a biomarker for allergy and asthma has been decidedly mixed, however, said Dr. Huang.

One study, for example, showed that lower sCD14 levels at birth were associated with increased risk of wheeze at age 1 (Am. J. Respir. Crit. Care Med. 2004;169:70-6), whereas a different study showed that sCD14 levels are higher during acute asthma episodes (Am. J. Respir. Care Crit. Med. 2006;173:617-22).

Because allergic diseases have been steadily rising in Taiwan since the 1970s, the investigators hoped to clarify whether sCD14 level at birth and/or the urine leukotriene E4 to creatinine (LC) ratio at 1 month could be useful predictors of an individual child’s risk for future atopic diseases and asthma.

They recruited newborns delivered at the Chang Chung Memorial Hospital from October 2007 through September 2009, recording sCD14 levels at birth and collecting questionnaires from the mothers asking about parental medical and allergic histories. The questionnaires were repeated at 1, 6, 12, and 18 months.

At 1 month they collected and examined urine for the LC ratio, and followed with child blood and urine samples at 6 and 12 months, and mother’s blood sample at 6 months.

They defined outcomes at age 1 as parental report of wheezing, cough persisting for more than 3 weeks, rhinitis (runny or blocked nose in the absence of a cold or flu), rhinoconjunctivitis, rash (intermittent for at least 3 months), and atopy (positive specific immunoglobulin E to Dermatophagoides pteronyssinus, D.farinae, egg white, milk, Cladosporium herbarum, and wheat).

Of the 206 children available for follow-up at 1 year, wheeze was prevalent in 14%), and sCD14 levels in these children were significantly higher than in the 177 children with no reported wheeze (583 plus or minus 127 vs. 491 plus or minus 162 ng/mL, P = .001).

Similarly, prolonged cough was reported in 7% at 1 year, and these children also had significantly higher sCD14 levels in cord blood (615 plus or minus 170 vs. 496 plus or minus 157, P = .008).

There were no other significant associations with sCD14 and other outcomes. LC ratio at 1 month was not significantly associated with any of the outcomes.

In multiple logistic regression analysis, they found that factors significantly predictive for wheeze at 1 year included sCD14 (P = .002), duration of day care attendance (P = .005), and parental smoking, with each pack per day of cigarettes associated with a doubling of risk (P = .016).

Significant risk factors for prolonged cough include sCD14 (P = .008) and number of older siblings (P = .015).

In a comparison of high vs. low sCD14, the adjusted odds ratio for wheeze with high levels was 7.74 (P less than .001). The adjusted OR for prolonged cough was 5.99 (P = .021).

The study was supported by a Chang Gung Research project grant. Dr. Huang reported that he had no relevant disclosures.

ORLANDO – Elevated levels of soluble CD14 in umbilical cord blood appear to be highly predictive of wheeze and cough in the first year of an infant’s life, Taiwanese investigators reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Children with elevated cord-blood soluble CD14 (sCD14) had nearly an eightfold risk for wheezing and a sixfold risk for cough in the first year, compared with children with low levels, said Dr. Yu-Lin Huang from the department of pediatrics at the Chang Gung Memorial Hospital and Chang Gung University in Keelung, Taiwan.

The finding lends credence to the hypothesis that prenatal factors play a role in the pathogenesis of asthma.

Soluble CD14 is a pathogen pattern receptor molecule that works with other receptors to recognize bacterial lipopolysaccharides (LPS) and mediate LPS-induced inflammation. Evidence for its utility as a biomarker for allergy and asthma has been decidedly mixed, however, said Dr. Huang.

One study, for example, showed that lower sCD14 levels at birth were associated with increased risk of wheeze at age 1 (Am. J. Respir. Crit. Care Med. 2004;169:70-6), whereas a different study showed that sCD14 levels are higher during acute asthma episodes (Am. J. Respir. Care Crit. Med. 2006;173:617-22).

Because allergic diseases have been steadily rising in Taiwan since the 1970s, the investigators hoped to clarify whether sCD14 level at birth and/or the urine leukotriene E4 to creatinine (LC) ratio at 1 month could be useful predictors of an individual child’s risk for future atopic diseases and asthma.

They recruited newborns delivered at the Chang Chung Memorial Hospital from October 2007 through September 2009, recording sCD14 levels at birth and collecting questionnaires from the mothers asking about parental medical and allergic histories. The questionnaires were repeated at 1, 6, 12, and 18 months.

At 1 month they collected and examined urine for the LC ratio, and followed with child blood and urine samples at 6 and 12 months, and mother’s blood sample at 6 months.

They defined outcomes at age 1 as parental report of wheezing, cough persisting for more than 3 weeks, rhinitis (runny or blocked nose in the absence of a cold or flu), rhinoconjunctivitis, rash (intermittent for at least 3 months), and atopy (positive specific immunoglobulin E to Dermatophagoides pteronyssinus, D.farinae, egg white, milk, Cladosporium herbarum, and wheat).

Of the 206 children available for follow-up at 1 year, wheeze was prevalent in 14%), and sCD14 levels in these children were significantly higher than in the 177 children with no reported wheeze (583 plus or minus 127 vs. 491 plus or minus 162 ng/mL, P = .001).

Similarly, prolonged cough was reported in 7% at 1 year, and these children also had significantly higher sCD14 levels in cord blood (615 plus or minus 170 vs. 496 plus or minus 157, P = .008).

There were no other significant associations with sCD14 and other outcomes. LC ratio at 1 month was not significantly associated with any of the outcomes.

In multiple logistic regression analysis, they found that factors significantly predictive for wheeze at 1 year included sCD14 (P = .002), duration of day care attendance (P = .005), and parental smoking, with each pack per day of cigarettes associated with a doubling of risk (P = .016).

Significant risk factors for prolonged cough include sCD14 (P = .008) and number of older siblings (P = .015).

In a comparison of high vs. low sCD14, the adjusted odds ratio for wheeze with high levels was 7.74 (P less than .001). The adjusted OR for prolonged cough was 5.99 (P = .021).

The study was supported by a Chang Gung Research project grant. Dr. Huang reported that he had no relevant disclosures.

ORLANDO – Vitamin D insufficiency at age 1 year was associated with a nearly fourfold increased prevalence of a food allergy in a case-control study of 269 children.

The finding appears consistent with prior reports that linked the prevalence of food allergies to the latitude gradients for where people lived, Dr. Katrina J. Allen and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Those reports had suggested that the further people lived from the equator, the higher their rate of hospitalizations for food-allergy related events, said Dr. Allen, a pediatric allergist and gastroenterologist at Royal Children’s Hospital Melbourne, and her associates.

The study involved 5,276 12-month old infants from the Melbourne area enrolled in the Health Nuts population-based study. All infants had skin prick tests to egg white, peanut, and sesame; 1,005 developed at least a 1 mm wheal to at least one of these foods. Of the 834 food-sensitized infants who returned to the clinic for an oral food challenge with egg, peanut, and sesame, 351 were identified as food allergic with at least three non-contact hives or areas of urticaria that persisted for at least 5 minutes; perioral or periorbital angioedema; or severe and persistent vomiting or anaphylaxis (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB141).

The researchers then drew blood specimens from 165 of the food-allergic infants and 104 control infants without food allergy or sensitivity, and measured their serum level of 25-hydroxyvitamin D.

In all, 92 of the control infants (88%) were vitamin D sufficient, with a serum level greater than 50 nM, corresponding to a level greater than 20 ng/mL. Among the infants with a food allergy, 118 (72%) were vitamin D sufficient (N. Engl. J. Med. 2011;364:248-54).

Vitamin D insufficiency, defined as a serum level of 26-50 nM (10 ng/mL to 20 ng/mL), occurred in 11% (11) of the control infants and in 25% (42) of the infants with a food allergy.

The remainder of the infants in the study, one in the control group and five in the food-allergy group, were vitamin D deficient, with a serum level of 25 nM or less (less than 10 ng/mL), but the numbers in this subgroup were too limited to allow a meaningful statistical analysis.

In a multiple logistical regression model that adjusted for diet (breast fed or formula fed), level of prior egg consumption, number of siblings, the presence of a pet dog, and ambient UV radiation exposure at the time of the blood draw, vitamin D insufficiency was linked with a statistically significant, 3.8-fold increased rate of food allergy, compared with the infants who were vitamin D sufficient, the researchers reported.

Dr. Allen and her associates said that they had no relevant financial disclosures.

ORLANDO – Vitamin D insufficiency at age 1 year was associated with a nearly fourfold increased prevalence of a food allergy in a case-control study of 269 children.

The finding appears consistent with prior reports that linked the prevalence of food allergies to the latitude gradients for where people lived, Dr. Katrina J. Allen and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Those reports had suggested that the further people lived from the equator, the higher their rate of hospitalizations for food-allergy related events, said Dr. Allen, a pediatric allergist and gastroenterologist at Royal Children’s Hospital Melbourne, and her associates.

The study involved 5,276 12-month old infants from the Melbourne area enrolled in the Health Nuts population-based study. All infants had skin prick tests to egg white, peanut, and sesame; 1,005 developed at least a 1 mm wheal to at least one of these foods. Of the 834 food-sensitized infants who returned to the clinic for an oral food challenge with egg, peanut, and sesame, 351 were identified as food allergic with at least three non-contact hives or areas of urticaria that persisted for at least 5 minutes; perioral or periorbital angioedema; or severe and persistent vomiting or anaphylaxis (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB141).

The researchers then drew blood specimens from 165 of the food-allergic infants and 104 control infants without food allergy or sensitivity, and measured their serum level of 25-hydroxyvitamin D.

In all, 92 of the control infants (88%) were vitamin D sufficient, with a serum level greater than 50 nM, corresponding to a level greater than 20 ng/mL. Among the infants with a food allergy, 118 (72%) were vitamin D sufficient (N. Engl. J. Med. 2011;364:248-54).

Vitamin D insufficiency, defined as a serum level of 26-50 nM (10 ng/mL to 20 ng/mL), occurred in 11% (11) of the control infants and in 25% (42) of the infants with a food allergy.

The remainder of the infants in the study, one in the control group and five in the food-allergy group, were vitamin D deficient, with a serum level of 25 nM or less (less than 10 ng/mL), but the numbers in this subgroup were too limited to allow a meaningful statistical analysis.

In a multiple logistical regression model that adjusted for diet (breast fed or formula fed), level of prior egg consumption, number of siblings, the presence of a pet dog, and ambient UV radiation exposure at the time of the blood draw, vitamin D insufficiency was linked with a statistically significant, 3.8-fold increased rate of food allergy, compared with the infants who were vitamin D sufficient, the researchers reported.

Dr. Allen and her associates said that they had no relevant financial disclosures.

ORLANDO – Vitamin D insufficiency at age 1 year was associated with a nearly fourfold increased prevalence of a food allergy in a case-control study of 269 children.

The finding appears consistent with prior reports that linked the prevalence of food allergies to the latitude gradients for where people lived, Dr. Katrina J. Allen and her associates reported in a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Those reports had suggested that the further people lived from the equator, the higher their rate of hospitalizations for food-allergy related events, said Dr. Allen, a pediatric allergist and gastroenterologist at Royal Children’s Hospital Melbourne, and her associates.

The study involved 5,276 12-month old infants from the Melbourne area enrolled in the Health Nuts population-based study. All infants had skin prick tests to egg white, peanut, and sesame; 1,005 developed at least a 1 mm wheal to at least one of these foods. Of the 834 food-sensitized infants who returned to the clinic for an oral food challenge with egg, peanut, and sesame, 351 were identified as food allergic with at least three non-contact hives or areas of urticaria that persisted for at least 5 minutes; perioral or periorbital angioedema; or severe and persistent vomiting or anaphylaxis (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB141).

The researchers then drew blood specimens from 165 of the food-allergic infants and 104 control infants without food allergy or sensitivity, and measured their serum level of 25-hydroxyvitamin D.

In all, 92 of the control infants (88%) were vitamin D sufficient, with a serum level greater than 50 nM, corresponding to a level greater than 20 ng/mL. Among the infants with a food allergy, 118 (72%) were vitamin D sufficient (N. Engl. J. Med. 2011;364:248-54).

Vitamin D insufficiency, defined as a serum level of 26-50 nM (10 ng/mL to 20 ng/mL), occurred in 11% (11) of the control infants and in 25% (42) of the infants with a food allergy.

The remainder of the infants in the study, one in the control group and five in the food-allergy group, were vitamin D deficient, with a serum level of 25 nM or less (less than 10 ng/mL), but the numbers in this subgroup were too limited to allow a meaningful statistical analysis.

In a multiple logistical regression model that adjusted for diet (breast fed or formula fed), level of prior egg consumption, number of siblings, the presence of a pet dog, and ambient UV radiation exposure at the time of the blood draw, vitamin D insufficiency was linked with a statistically significant, 3.8-fold increased rate of food allergy, compared with the infants who were vitamin D sufficient, the researchers reported.

Dr. Allen and her associates said that they had no relevant financial disclosures.

ORLANDO – School children with asthma who also have a food allergy have a significantly increased need for controller drugs and hospitalization, compared with similar asthmatic children without a food allergy, based on data collected from 302 U.S. patients.

Food allergies are also "highly prevalent" among U.S. school children with asthma in inner-city neighborhoods, affecting a quarter of the children enrolled in the School Inner City Asthma Study, Dr. James L. Friedlander said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Photo: mates/Fotolia.com

Multiple food allergies produced even more pronounced exacerbations, linking with "a higher risk of more severe asthma morbidity and more resource use," said Dr. Friedlander, an allergy and immunology physician at Children’s Hospital Boston.

The School Inner City Asthma Study enrolled 302 children aged 5-13 from about 20 schools in the northeastern United States. All children had physician-diagnosed asthma, plus at least one of these three markers of significant disease: at least one wheezing episode during the prior 12 months, need for daily preventive medical treatment, or at least one unscheduled visit to a physicians for asthma during the prior 12 months. The average age of the enrolled children was 8, and they divided equally as boys and girls. About a third of the children were black, a third were Hispanic, 5% were white, and the remainder were other racial and ethnic groups. Nearly three quarters came from households with an annual income of less than $45,000, and 80% had a family history of asthma (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB132).

In all, 75 of the children (25%) had a food allergy documented by testing at their entry into the study, and 36 of these children were allergic to more than one food. The most common food allergy was to peanut (43%), followed by tree nut (29%), fruit (25%), shellfish (21%), egg (17%), milk (15%), soy (10%), and fish (10%).

About half of the children also had a diagnosis of eczema. Among the children with a food allergy, symptoms generally appeared within an hour of eating the allergic food. This resulted in urticaria in 60%, mouth or throat itching in 44%, and swelling in 40%. But many of the children also displayed respiratory symptoms as their allergic response to food, with 33% having difficulty breathing, 31% experiencing throat tightening, 29% wheezing, and 28% coughing.

Questionnaire replies from the children’s parents identified several features of exacerbated asthma in the children with food allergies. Among those with a food allergy, 73% used a controller medication, compared with a 58% rate among the children without a food allergy, a statistically significant difference. The food-allergic children had a 63% lifetime rate of having been hospitalized at least once, compared with a 40% rate among the children without a food allergy, a statistically significant difference.

Among the 36 children with two or more food allergies, 78% had a history of hospitalization, and 78% used controller medications. Also among the kids with multiple food allergies, 17% had been hospitalized within the 12 months prior to the survey of their parents, compared with a 7% rate among the children with asthma and no food allergy.

Other statistically significant indications of worse asthma morbidity in the children with multiple food allergies included 42% with at least 3 days of asthma symptoms during the preceding 2 weeks, compared with 22% among the children with no food allergy, and a mean number of 5.8 clinic or emergency department visits during the prior 12 months, compared with an average of 4.1 visits among the children with no food allergies.

Dr. Friedlander said that he had no relevant financial disclosures.

ORLANDO – School children with asthma who also have a food allergy have a significantly increased need for controller drugs and hospitalization, compared with similar asthmatic children without a food allergy, based on data collected from 302 U.S. patients.

Food allergies are also "highly prevalent" among U.S. school children with asthma in inner-city neighborhoods, affecting a quarter of the children enrolled in the School Inner City Asthma Study, Dr. James L. Friedlander said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Photo: mates/Fotolia.com

Multiple food allergies produced even more pronounced exacerbations, linking with "a higher risk of more severe asthma morbidity and more resource use," said Dr. Friedlander, an allergy and immunology physician at Children’s Hospital Boston.

The School Inner City Asthma Study enrolled 302 children aged 5-13 from about 20 schools in the northeastern United States. All children had physician-diagnosed asthma, plus at least one of these three markers of significant disease: at least one wheezing episode during the prior 12 months, need for daily preventive medical treatment, or at least one unscheduled visit to a physicians for asthma during the prior 12 months. The average age of the enrolled children was 8, and they divided equally as boys and girls. About a third of the children were black, a third were Hispanic, 5% were white, and the remainder were other racial and ethnic groups. Nearly three quarters came from households with an annual income of less than $45,000, and 80% had a family history of asthma (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB132).

In all, 75 of the children (25%) had a food allergy documented by testing at their entry into the study, and 36 of these children were allergic to more than one food. The most common food allergy was to peanut (43%), followed by tree nut (29%), fruit (25%), shellfish (21%), egg (17%), milk (15%), soy (10%), and fish (10%).

About half of the children also had a diagnosis of eczema. Among the children with a food allergy, symptoms generally appeared within an hour of eating the allergic food. This resulted in urticaria in 60%, mouth or throat itching in 44%, and swelling in 40%. But many of the children also displayed respiratory symptoms as their allergic response to food, with 33% having difficulty breathing, 31% experiencing throat tightening, 29% wheezing, and 28% coughing.

Questionnaire replies from the children’s parents identified several features of exacerbated asthma in the children with food allergies. Among those with a food allergy, 73% used a controller medication, compared with a 58% rate among the children without a food allergy, a statistically significant difference. The food-allergic children had a 63% lifetime rate of having been hospitalized at least once, compared with a 40% rate among the children without a food allergy, a statistically significant difference.

Among the 36 children with two or more food allergies, 78% had a history of hospitalization, and 78% used controller medications. Also among the kids with multiple food allergies, 17% had been hospitalized within the 12 months prior to the survey of their parents, compared with a 7% rate among the children with asthma and no food allergy.

Other statistically significant indications of worse asthma morbidity in the children with multiple food allergies included 42% with at least 3 days of asthma symptoms during the preceding 2 weeks, compared with 22% among the children with no food allergy, and a mean number of 5.8 clinic or emergency department visits during the prior 12 months, compared with an average of 4.1 visits among the children with no food allergies.

Dr. Friedlander said that he had no relevant financial disclosures.

ORLANDO – School children with asthma who also have a food allergy have a significantly increased need for controller drugs and hospitalization, compared with similar asthmatic children without a food allergy, based on data collected from 302 U.S. patients.

Food allergies are also "highly prevalent" among U.S. school children with asthma in inner-city neighborhoods, affecting a quarter of the children enrolled in the School Inner City Asthma Study, Dr. James L. Friedlander said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Photo: mates/Fotolia.com

Multiple food allergies produced even more pronounced exacerbations, linking with "a higher risk of more severe asthma morbidity and more resource use," said Dr. Friedlander, an allergy and immunology physician at Children’s Hospital Boston.

The School Inner City Asthma Study enrolled 302 children aged 5-13 from about 20 schools in the northeastern United States. All children had physician-diagnosed asthma, plus at least one of these three markers of significant disease: at least one wheezing episode during the prior 12 months, need for daily preventive medical treatment, or at least one unscheduled visit to a physicians for asthma during the prior 12 months. The average age of the enrolled children was 8, and they divided equally as boys and girls. About a third of the children were black, a third were Hispanic, 5% were white, and the remainder were other racial and ethnic groups. Nearly three quarters came from households with an annual income of less than $45,000, and 80% had a family history of asthma (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB132).

In all, 75 of the children (25%) had a food allergy documented by testing at their entry into the study, and 36 of these children were allergic to more than one food. The most common food allergy was to peanut (43%), followed by tree nut (29%), fruit (25%), shellfish (21%), egg (17%), milk (15%), soy (10%), and fish (10%).

About half of the children also had a diagnosis of eczema. Among the children with a food allergy, symptoms generally appeared within an hour of eating the allergic food. This resulted in urticaria in 60%, mouth or throat itching in 44%, and swelling in 40%. But many of the children also displayed respiratory symptoms as their allergic response to food, with 33% having difficulty breathing, 31% experiencing throat tightening, 29% wheezing, and 28% coughing.

Questionnaire replies from the children’s parents identified several features of exacerbated asthma in the children with food allergies. Among those with a food allergy, 73% used a controller medication, compared with a 58% rate among the children without a food allergy, a statistically significant difference. The food-allergic children had a 63% lifetime rate of having been hospitalized at least once, compared with a 40% rate among the children without a food allergy, a statistically significant difference.

Among the 36 children with two or more food allergies, 78% had a history of hospitalization, and 78% used controller medications. Also among the kids with multiple food allergies, 17% had been hospitalized within the 12 months prior to the survey of their parents, compared with a 7% rate among the children with asthma and no food allergy.

Other statistically significant indications of worse asthma morbidity in the children with multiple food allergies included 42% with at least 3 days of asthma symptoms during the preceding 2 weeks, compared with 22% among the children with no food allergy, and a mean number of 5.8 clinic or emergency department visits during the prior 12 months, compared with an average of 4.1 visits among the children with no food allergies.

Dr. Friedlander said that he had no relevant financial disclosures.

The benefits of routine lung cancer screening in high-risk individuals outweigh the potential risks, according to members of a National Comprehensive Cancer Network guidelines panel that recommended low-dose helical CT screening of two high-risk groups.

Mary E. Reid, Ph.D., of the Roswell Park Cancer Institute in Buffalo, N.Y., acknowledged the burdens – in particular, the cost and requisite resource utilization – associated with following all high-risk patients who screen positive. But, she said, "the evidence [in favor of] the recommendations is really strong and supports their implementation."

Lung cancer, she noted, is the only one of the top four deadliest cancers (lung, prostate, breast, and colorectal) that is not currently subject to routine screening.

Dr. Reid and colleagues on the National Comprehensive Cancer Network (NCCN) Guidelines Panel for Lung Cancer Screening presented the update at the NCCN annual conference March 14-18 in Hollywood, Fla. It had been issued in October 2011 and followed a New England Journal of Medicine report that low-dose CT screening of heavy smokers reduced lung cancer mortality by 20%, compared with annual chest x-rays, in the National Lung Screening Trial (NLST).

The revised guidelines recommend annual low-dose helical CT screening for the following two groups of high-risk individuals:

• Those aged 55-74 years with a minimum smoking history of 30 pack-years who either are current smokers or quit within the past 15 years.

• Those aged 50 years or older with a minimum smoking history of 20 pack-years plus one additional lung cancer risk factor, excluding secondhand smoke exposure.

Evidence from the randomized, controlled NLST suggests that early detection via screening reduced lung-cancer specific mortality in the former risk group, which characterizes the NLST patient population. Specifically, 1 in 100 high-risk individuals who were enrolled in the study screened positive on their first low-dose CT exam, and one life was saved for every 320 high-risk individuals screened over 2 years (three screens) (N. Engl. J. Med. 2011;365:395-409). The NCCN recommendation for this group is category 1, the highest level.

The recommendation for annual screening in the second high-risk group is based on less-robust evidence and a nonuniform consensus of the NCCN panel members, Dr. Reid said. As such, it is a less-emphatic category 2B recommendation.

The NCCN screening recommendations have been deemed by some experts to be premature in the absence of cost-efficacy analysis, particularly because of the high false-positive rates observed in both the CT group (96.4%) and the radiography group (94.5%), as well as the potentially harmful effects of radiation exposure associated with low-dose CT screening.

Despite the favorable outcome of their study, the NLST authors stressed the need for rigorous cost-effectiveness analyses before the crafting of public policy recommendations. "The reductions in lung-cancer mortality must be weighed against the harms from positive screening results and overdiagnosis, as well as the costs," they wrote. "The cost component of low-dose CT screening includes not only the screening examination itself but also the diagnostic follow-up and treatment."

In addition to recommending appropriate candidates for routine screening and the proposed frequency of the scans, the new NCCN guidelines outline lung cancer risk factors, address the risks and benefits of screening as well as screening accuracy, and offer an algorithm for the evaluation and follow-up of positive screens.

Specifically, the guidelines recommend the following:

• Basing the frequency of low-dose CT in high-risk patients on the size and status (solid, nonsolid, part-solid, ground-glass, ground-glass opacity) of the nodule on baseline CT.

• Excising all nodules that increase in size or become solid or part-solid during follow-up.

• Considering PET with CT for nodules 8 mm or larger at baseline.

• Performing biopsy or excision of nodules that are suspicious for lung cancer, based on PET with CT findings.

• Reexamining within 1 month solid endobronchial nodules with low-dose CT immediately after vigorous coughing.

• Counseling smokers to quit.

The NCCN is the first professional organization to recommend routine low-dose CT screening for individuals who are considered to be at high-risk for lung cancer, according to Dr. Reid. Last summer, the International Association for the Study of Lung Cancer issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of those enrolled in the NSLT.

Dr. Reid disclosed no financial conflicts of interest. Disclosures of the NCCN Guidelines Panel for Lung Cancer Screening are online. 

The benefits of routine lung cancer screening in high-risk individuals outweigh the potential risks, according to members of a National Comprehensive Cancer Network guidelines panel that recommended low-dose helical CT screening of two high-risk groups.

Mary E. Reid, Ph.D., of the Roswell Park Cancer Institute in Buffalo, N.Y., acknowledged the burdens – in particular, the cost and requisite resource utilization – associated with following all high-risk patients who screen positive. But, she said, "the evidence [in favor of] the recommendations is really strong and supports their implementation."

Lung cancer, she noted, is the only one of the top four deadliest cancers (lung, prostate, breast, and colorectal) that is not currently subject to routine screening.

Dr. Reid and colleagues on the National Comprehensive Cancer Network (NCCN) Guidelines Panel for Lung Cancer Screening presented the update at the NCCN annual conference March 14-18 in Hollywood, Fla. It had been issued in October 2011 and followed a New England Journal of Medicine report that low-dose CT screening of heavy smokers reduced lung cancer mortality by 20%, compared with annual chest x-rays, in the National Lung Screening Trial (NLST).

The revised guidelines recommend annual low-dose helical CT screening for the following two groups of high-risk individuals:

• Those aged 55-74 years with a minimum smoking history of 30 pack-years who either are current smokers or quit within the past 15 years.

• Those aged 50 years or older with a minimum smoking history of 20 pack-years plus one additional lung cancer risk factor, excluding secondhand smoke exposure.

Evidence from the randomized, controlled NLST suggests that early detection via screening reduced lung-cancer specific mortality in the former risk group, which characterizes the NLST patient population. Specifically, 1 in 100 high-risk individuals who were enrolled in the study screened positive on their first low-dose CT exam, and one life was saved for every 320 high-risk individuals screened over 2 years (three screens) (N. Engl. J. Med. 2011;365:395-409). The NCCN recommendation for this group is category 1, the highest level.

The recommendation for annual screening in the second high-risk group is based on less-robust evidence and a nonuniform consensus of the NCCN panel members, Dr. Reid said. As such, it is a less-emphatic category 2B recommendation.

The NCCN screening recommendations have been deemed by some experts to be premature in the absence of cost-efficacy analysis, particularly because of the high false-positive rates observed in both the CT group (96.4%) and the radiography group (94.5%), as well as the potentially harmful effects of radiation exposure associated with low-dose CT screening.

Despite the favorable outcome of their study, the NLST authors stressed the need for rigorous cost-effectiveness analyses before the crafting of public policy recommendations. "The reductions in lung-cancer mortality must be weighed against the harms from positive screening results and overdiagnosis, as well as the costs," they wrote. "The cost component of low-dose CT screening includes not only the screening examination itself but also the diagnostic follow-up and treatment."

In addition to recommending appropriate candidates for routine screening and the proposed frequency of the scans, the new NCCN guidelines outline lung cancer risk factors, address the risks and benefits of screening as well as screening accuracy, and offer an algorithm for the evaluation and follow-up of positive screens.

Specifically, the guidelines recommend the following:

• Basing the frequency of low-dose CT in high-risk patients on the size and status (solid, nonsolid, part-solid, ground-glass, ground-glass opacity) of the nodule on baseline CT.

• Excising all nodules that increase in size or become solid or part-solid during follow-up.

• Considering PET with CT for nodules 8 mm or larger at baseline.

• Performing biopsy or excision of nodules that are suspicious for lung cancer, based on PET with CT findings.

• Reexamining within 1 month solid endobronchial nodules with low-dose CT immediately after vigorous coughing.

• Counseling smokers to quit.

The NCCN is the first professional organization to recommend routine low-dose CT screening for individuals who are considered to be at high-risk for lung cancer, according to Dr. Reid. Last summer, the International Association for the Study of Lung Cancer issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of those enrolled in the NSLT.

Dr. Reid disclosed no financial conflicts of interest. Disclosures of the NCCN Guidelines Panel for Lung Cancer Screening are online. 

The benefits of routine lung cancer screening in high-risk individuals outweigh the potential risks, according to members of a National Comprehensive Cancer Network guidelines panel that recommended low-dose helical CT screening of two high-risk groups.

Mary E. Reid, Ph.D., of the Roswell Park Cancer Institute in Buffalo, N.Y., acknowledged the burdens – in particular, the cost and requisite resource utilization – associated with following all high-risk patients who screen positive. But, she said, "the evidence [in favor of] the recommendations is really strong and supports their implementation."

Lung cancer, she noted, is the only one of the top four deadliest cancers (lung, prostate, breast, and colorectal) that is not currently subject to routine screening.

Dr. Reid and colleagues on the National Comprehensive Cancer Network (NCCN) Guidelines Panel for Lung Cancer Screening presented the update at the NCCN annual conference March 14-18 in Hollywood, Fla. It had been issued in October 2011 and followed a New England Journal of Medicine report that low-dose CT screening of heavy smokers reduced lung cancer mortality by 20%, compared with annual chest x-rays, in the National Lung Screening Trial (NLST).

The revised guidelines recommend annual low-dose helical CT screening for the following two groups of high-risk individuals:

• Those aged 55-74 years with a minimum smoking history of 30 pack-years who either are current smokers or quit within the past 15 years.

• Those aged 50 years or older with a minimum smoking history of 20 pack-years plus one additional lung cancer risk factor, excluding secondhand smoke exposure.

Evidence from the randomized, controlled NLST suggests that early detection via screening reduced lung-cancer specific mortality in the former risk group, which characterizes the NLST patient population. Specifically, 1 in 100 high-risk individuals who were enrolled in the study screened positive on their first low-dose CT exam, and one life was saved for every 320 high-risk individuals screened over 2 years (three screens) (N. Engl. J. Med. 2011;365:395-409). The NCCN recommendation for this group is category 1, the highest level.

The recommendation for annual screening in the second high-risk group is based on less-robust evidence and a nonuniform consensus of the NCCN panel members, Dr. Reid said. As such, it is a less-emphatic category 2B recommendation.

The NCCN screening recommendations have been deemed by some experts to be premature in the absence of cost-efficacy analysis, particularly because of the high false-positive rates observed in both the CT group (96.4%) and the radiography group (94.5%), as well as the potentially harmful effects of radiation exposure associated with low-dose CT screening.

Despite the favorable outcome of their study, the NLST authors stressed the need for rigorous cost-effectiveness analyses before the crafting of public policy recommendations. "The reductions in lung-cancer mortality must be weighed against the harms from positive screening results and overdiagnosis, as well as the costs," they wrote. "The cost component of low-dose CT screening includes not only the screening examination itself but also the diagnostic follow-up and treatment."

In addition to recommending appropriate candidates for routine screening and the proposed frequency of the scans, the new NCCN guidelines outline lung cancer risk factors, address the risks and benefits of screening as well as screening accuracy, and offer an algorithm for the evaluation and follow-up of positive screens.

Specifically, the guidelines recommend the following:

• Basing the frequency of low-dose CT in high-risk patients on the size and status (solid, nonsolid, part-solid, ground-glass, ground-glass opacity) of the nodule on baseline CT.

• Excising all nodules that increase in size or become solid or part-solid during follow-up.

• Considering PET with CT for nodules 8 mm or larger at baseline.

• Performing biopsy or excision of nodules that are suspicious for lung cancer, based on PET with CT findings.

• Reexamining within 1 month solid endobronchial nodules with low-dose CT immediately after vigorous coughing.

• Counseling smokers to quit.

The NCCN is the first professional organization to recommend routine low-dose CT screening for individuals who are considered to be at high-risk for lung cancer, according to Dr. Reid. Last summer, the International Association for the Study of Lung Cancer issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of those enrolled in the NSLT.

Dr. Reid disclosed no financial conflicts of interest. Disclosures of the NCCN Guidelines Panel for Lung Cancer Screening are online. 

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

ORLANDO – A chart notation of "lost to follow-up" can mean loss of life for children with severe asthma, suggest the results of a retrospective study reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 14 children who died from asthma at a children’s hospital over a 10-year period, 11 (79%) evidently never received follow-up care in the asthma clinic, despite having prior asthma-related hospitalizations and clinic appointments made at the time of discharge, reported Dr. Sahar Faghih, a second-year fellow in allergy and immunology at Children’s Hospital of Michigan in Detroit.

"Deaths of high-risk asthmatics were decreased by a combination of a multidisciplinary team clinic and a social service liaison for increased family support. This further emphasizes that barriers to care and clinic attendance necessitate further attention," Dr. Faghih and her colleagues wrote in a poster.

The investigators reviewed a decade of charts on children aged 1-18 years who died from asthma in the period spanning 3 years before to 7 years after the multidisciplinary Children’s Hospital Asthma Management Program (CHAMP) clinic opened in 2004. The social service component of the multidisciplinary team was phased out after 3 years due to lack of funding.

"Deaths of high-risk asthmatics were decreased by a combination of a multi-disciplinary team clinic and a social service liaison for increased family support."

Five of the 14 deaths occurred before the CHAMP clinic model was implemented, and none of these children were enrolled in a health plan. No deaths occurred during the 3 years that a social worker was present in the clinic.

"With the children who died in the care of the asthma clinic, there were some issues of adherence, and two out of five deaths that occurred between 2007 and 2010 occurred in patients who were previously enrolled in CHAMP. Both of those children had a history of medical neglect cases on file with the state," Dr. Faghih said in an interview.

"Perhaps if this clinic still had in place the social service intervention, we may have been able to prevent those deaths from happening," she added.

Although the multidisciplinary model was developed in a specialty children’s hospital, it can be replicated in community practices. Other studies have shown that programs coordinated by trained clinical nurses or nurse practitioners that include asthma education, emphasis on adherence, home visits, and telephone contacts can reduce asthma hospitalizations and emergency department visits by 71%-85%, Dr. Faghih said.

Team-based asthma education and case management programs can save money as well as lives, the investigators noted. They cited a randomized study showing that such programs reduced emergency department visits by 57%, hospitalizations by 75%, and expenditures by 71%. The same study estimated that for every dollar spent on a dedicated asthma nurse, $7.69-$11.76 was saved (J. Allergy Clin. Immunol. 1999;103:436-40).

"Based on 2008 CDC [Centers for Disease Control and Prevention] reporting, there have been a total of 200 pediatric asthma deaths. Perhaps, with the implementation of a multiteam approach, this number can be rectified," Dr. Faghih and her colleagues wrote.

The study was internally funded. The authors reported that they had no conflicts of interest.

ORLANDO – A chart notation of "lost to follow-up" can mean loss of life for children with severe asthma, suggest the results of a retrospective study reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 14 children who died from asthma at a children’s hospital over a 10-year period, 11 (79%) evidently never received follow-up care in the asthma clinic, despite having prior asthma-related hospitalizations and clinic appointments made at the time of discharge, reported Dr. Sahar Faghih, a second-year fellow in allergy and immunology at Children’s Hospital of Michigan in Detroit.

"Deaths of high-risk asthmatics were decreased by a combination of a multidisciplinary team clinic and a social service liaison for increased family support. This further emphasizes that barriers to care and clinic attendance necessitate further attention," Dr. Faghih and her colleagues wrote in a poster.

The investigators reviewed a decade of charts on children aged 1-18 years who died from asthma in the period spanning 3 years before to 7 years after the multidisciplinary Children’s Hospital Asthma Management Program (CHAMP) clinic opened in 2004. The social service component of the multidisciplinary team was phased out after 3 years due to lack of funding.

"Deaths of high-risk asthmatics were decreased by a combination of a multi-disciplinary team clinic and a social service liaison for increased family support."

Five of the 14 deaths occurred before the CHAMP clinic model was implemented, and none of these children were enrolled in a health plan. No deaths occurred during the 3 years that a social worker was present in the clinic.

"With the children who died in the care of the asthma clinic, there were some issues of adherence, and two out of five deaths that occurred between 2007 and 2010 occurred in patients who were previously enrolled in CHAMP. Both of those children had a history of medical neglect cases on file with the state," Dr. Faghih said in an interview.

"Perhaps if this clinic still had in place the social service intervention, we may have been able to prevent those deaths from happening," she added.

Although the multidisciplinary model was developed in a specialty children’s hospital, it can be replicated in community practices. Other studies have shown that programs coordinated by trained clinical nurses or nurse practitioners that include asthma education, emphasis on adherence, home visits, and telephone contacts can reduce asthma hospitalizations and emergency department visits by 71%-85%, Dr. Faghih said.

Team-based asthma education and case management programs can save money as well as lives, the investigators noted. They cited a randomized study showing that such programs reduced emergency department visits by 57%, hospitalizations by 75%, and expenditures by 71%. The same study estimated that for every dollar spent on a dedicated asthma nurse, $7.69-$11.76 was saved (J. Allergy Clin. Immunol. 1999;103:436-40).

"Based on 2008 CDC [Centers for Disease Control and Prevention] reporting, there have been a total of 200 pediatric asthma deaths. Perhaps, with the implementation of a multiteam approach, this number can be rectified," Dr. Faghih and her colleagues wrote.

The study was internally funded. The authors reported that they had no conflicts of interest.

ORLANDO – A chart notation of "lost to follow-up" can mean loss of life for children with severe asthma, suggest the results of a retrospective study reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Of 14 children who died from asthma at a children’s hospital over a 10-year period, 11 (79%) evidently never received follow-up care in the asthma clinic, despite having prior asthma-related hospitalizations and clinic appointments made at the time of discharge, reported Dr. Sahar Faghih, a second-year fellow in allergy and immunology at Children’s Hospital of Michigan in Detroit.

"Deaths of high-risk asthmatics were decreased by a combination of a multidisciplinary team clinic and a social service liaison for increased family support. This further emphasizes that barriers to care and clinic attendance necessitate further attention," Dr. Faghih and her colleagues wrote in a poster.

The investigators reviewed a decade of charts on children aged 1-18 years who died from asthma in the period spanning 3 years before to 7 years after the multidisciplinary Children’s Hospital Asthma Management Program (CHAMP) clinic opened in 2004. The social service component of the multidisciplinary team was phased out after 3 years due to lack of funding.

"Deaths of high-risk asthmatics were decreased by a combination of a multi-disciplinary team clinic and a social service liaison for increased family support."

Five of the 14 deaths occurred before the CHAMP clinic model was implemented, and none of these children were enrolled in a health plan. No deaths occurred during the 3 years that a social worker was present in the clinic.

"With the children who died in the care of the asthma clinic, there were some issues of adherence, and two out of five deaths that occurred between 2007 and 2010 occurred in patients who were previously enrolled in CHAMP. Both of those children had a history of medical neglect cases on file with the state," Dr. Faghih said in an interview.

"Perhaps if this clinic still had in place the social service intervention, we may have been able to prevent those deaths from happening," she added.

Although the multidisciplinary model was developed in a specialty children’s hospital, it can be replicated in community practices. Other studies have shown that programs coordinated by trained clinical nurses or nurse practitioners that include asthma education, emphasis on adherence, home visits, and telephone contacts can reduce asthma hospitalizations and emergency department visits by 71%-85%, Dr. Faghih said.

Team-based asthma education and case management programs can save money as well as lives, the investigators noted. They cited a randomized study showing that such programs reduced emergency department visits by 57%, hospitalizations by 75%, and expenditures by 71%. The same study estimated that for every dollar spent on a dedicated asthma nurse, $7.69-$11.76 was saved (J. Allergy Clin. Immunol. 1999;103:436-40).

"Based on 2008 CDC [Centers for Disease Control and Prevention] reporting, there have been a total of 200 pediatric asthma deaths. Perhaps, with the implementation of a multiteam approach, this number can be rectified," Dr. Faghih and her colleagues wrote.

The study was internally funded. The authors reported that they had no conflicts of interest.

MIAMI BEACH – Before you refer one of your pediatric patients with chronic rhinosinusitis to surgery, consider a trial of once-daily intranasal irrigation with isotonic saline, a pediatric otolaryngologist recommended, based on personal experience and results of a study with 40 children.

Participants in the 6-week study – children aged a mean 6 years – complied with the irrigation and experienced significant improvements in quality of life scores within 3 weeks. Prior to treatment, these children have "significant nasal stuffiness, and no matter how hard they blow their nose, nothing comes out," Dr. Julie L. Wei said.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis," Dr. Wei said. "Young children tolerate and like irrigation."

In the prospective, double-blind study, 19 children with chronic rhinosinusitis were randomized to daily irrigation with 80 mL saline only and 21 were randomized to 80 mL saline plus gentamicin. Congestion and cough were the most common presenting symptoms. The average duration of symptoms exceeded 8 weeks.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis."

With no significant difference in clinical improvement between the two groups at 3 and 6 weeks follow-up, results suggest that saline alone is efficacious, Dr. Wei said at the Triological Society Combined Sections Meeting.

"I had learned to use saline with gentamicin in it to irrigate adults, so I started to use it in children. I knew the [amount of] gentamicin in the saline was minuscule, and I wanted to prove to myself that saline would be just as efficacious," said Dr. Wei, who is on the otolaryngology–head and neck surgery faculty at the University of Kansas/KU Medical Center in Kansas City.

Symptom resolution post irrigation correlated with positive changes in Lund-MacKay scoring of before and after CT scans. All domains of the Sinus and Nasal Quality of Life Survey (SN5) significantly improved in both groups from baseline to 3 weeks, with continued improvements observed until 6 weeks. Full study results were published in September 2011 (Laryngoscope 2011;121:1989-2000).

One patient required functional endoscopic sinus surgery because of persistent symptoms. Four families reported otalgia during the study.

More than 90% of the children were compliant with the 6-week regimen and nasal irrigation was "absolutely safe," Dr. Wei said at the meeting, which was cosponsored by the Triological Society and the American College of Surgeons. In addition, children and families only require about 2 minutes of instruction in the technique.

Dr. Wei said that she had no relevant financial disclosures.

MIAMI BEACH – Before you refer one of your pediatric patients with chronic rhinosinusitis to surgery, consider a trial of once-daily intranasal irrigation with isotonic saline, a pediatric otolaryngologist recommended, based on personal experience and results of a study with 40 children.

Participants in the 6-week study – children aged a mean 6 years – complied with the irrigation and experienced significant improvements in quality of life scores within 3 weeks. Prior to treatment, these children have "significant nasal stuffiness, and no matter how hard they blow their nose, nothing comes out," Dr. Julie L. Wei said.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis," Dr. Wei said. "Young children tolerate and like irrigation."

In the prospective, double-blind study, 19 children with chronic rhinosinusitis were randomized to daily irrigation with 80 mL saline only and 21 were randomized to 80 mL saline plus gentamicin. Congestion and cough were the most common presenting symptoms. The average duration of symptoms exceeded 8 weeks.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis."

With no significant difference in clinical improvement between the two groups at 3 and 6 weeks follow-up, results suggest that saline alone is efficacious, Dr. Wei said at the Triological Society Combined Sections Meeting.

"I had learned to use saline with gentamicin in it to irrigate adults, so I started to use it in children. I knew the [amount of] gentamicin in the saline was minuscule, and I wanted to prove to myself that saline would be just as efficacious," said Dr. Wei, who is on the otolaryngology–head and neck surgery faculty at the University of Kansas/KU Medical Center in Kansas City.

Symptom resolution post irrigation correlated with positive changes in Lund-MacKay scoring of before and after CT scans. All domains of the Sinus and Nasal Quality of Life Survey (SN5) significantly improved in both groups from baseline to 3 weeks, with continued improvements observed until 6 weeks. Full study results were published in September 2011 (Laryngoscope 2011;121:1989-2000).

One patient required functional endoscopic sinus surgery because of persistent symptoms. Four families reported otalgia during the study.

More than 90% of the children were compliant with the 6-week regimen and nasal irrigation was "absolutely safe," Dr. Wei said at the meeting, which was cosponsored by the Triological Society and the American College of Surgeons. In addition, children and families only require about 2 minutes of instruction in the technique.

Dr. Wei said that she had no relevant financial disclosures.

MIAMI BEACH – Before you refer one of your pediatric patients with chronic rhinosinusitis to surgery, consider a trial of once-daily intranasal irrigation with isotonic saline, a pediatric otolaryngologist recommended, based on personal experience and results of a study with 40 children.

Participants in the 6-week study – children aged a mean 6 years – complied with the irrigation and experienced significant improvements in quality of life scores within 3 weeks. Prior to treatment, these children have "significant nasal stuffiness, and no matter how hard they blow their nose, nothing comes out," Dr. Julie L. Wei said.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis," Dr. Wei said. "Young children tolerate and like irrigation."

In the prospective, double-blind study, 19 children with chronic rhinosinusitis were randomized to daily irrigation with 80 mL saline only and 21 were randomized to 80 mL saline plus gentamicin. Congestion and cough were the most common presenting symptoms. The average duration of symptoms exceeded 8 weeks.

"Nasal irrigation is effective as first-line and possibly the only treatment for chronic rhinosinusitis."

With no significant difference in clinical improvement between the two groups at 3 and 6 weeks follow-up, results suggest that saline alone is efficacious, Dr. Wei said at the Triological Society Combined Sections Meeting.

"I had learned to use saline with gentamicin in it to irrigate adults, so I started to use it in children. I knew the [amount of] gentamicin in the saline was minuscule, and I wanted to prove to myself that saline would be just as efficacious," said Dr. Wei, who is on the otolaryngology–head and neck surgery faculty at the University of Kansas/KU Medical Center in Kansas City.

Symptom resolution post irrigation correlated with positive changes in Lund-MacKay scoring of before and after CT scans. All domains of the Sinus and Nasal Quality of Life Survey (SN5) significantly improved in both groups from baseline to 3 weeks, with continued improvements observed until 6 weeks. Full study results were published in September 2011 (Laryngoscope 2011;121:1989-2000).

One patient required functional endoscopic sinus surgery because of persistent symptoms. Four families reported otalgia during the study.

More than 90% of the children were compliant with the 6-week regimen and nasal irrigation was "absolutely safe," Dr. Wei said at the meeting, which was cosponsored by the Triological Society and the American College of Surgeons. In addition, children and families only require about 2 minutes of instruction in the technique.

Dr. Wei said that she had no relevant financial disclosures.

Exposure to diesel exhaust increases the risk of developing and dying from lung cancer, according to the results of a large cohort mortality study in more than 12,000 exposed workers and a related nested case-control study.

The Diesel Exhaust in Miners Study confirms prior studies demonstrating a possible causal relationship between diesel exhaust exposure and lung cancer, and suggests that this association represents an important public health burden in urban areas worldwide.

Both studies were published online March 5 in the Journal of the National Cancer Institute.

In the main cohort mortality study, the standardized mortality ratio (SMR) of 1.26 for lung cancer among 12,315 exposed workers was significantly greater than were state-based mortality rates, wrote Michael D. Attfield. Ph.D., formerly with the National Institute for Occupational Safety and Health in Morgantown, W.Va., and his colleagues.

Esophageal cancer and pneumoconiosis mortality also were significantly elevated in the exposed workers (SMRs, 1.83 and 12.20, respectively), the researchers found (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs035]).

Outcomes were evaluated in workers exposed to diesel exhaust at eight nonmetal mining facilities in the United States using retrospective quantitative estimates of respirable elemental carbon (REC) exposures as a surrogate for diesel exhaust exposure. The data covered the periods from the introduction (between 1947 and 1967) of diesel-powered equipment to 1997.

A dose-response relationship between exposure and lung cancer mortality was not apparent in the overall cohort, but clear evidence of such a relationship emerged after the investigators divided the population, comparing those who had worked underground at some point (ever-underground) with surface workers.

"In contrast to the complete cohort, hazard ratios that increased with level of exposure were seen for ever-underground workers using quartiles of REC exposure. Using the expanded exposure categories, hazard ratios for 15-year lagged cumulative REC exposure rose with increasing exposure, the trend being more pronounced when workers with shorter tenures were excluded," the investigators said.

As for the surface-only workers, no clear exposure-response trend was seen in the quartile analysis, but there was evidence of an increasing trend in risk with increasing exposure, they said.

The overall findings were "essentially unchanged" after the researchers controlled for cumulative exposures to silica, asbestos, nondiesel exhaust polycyclic aromatic hydrocarbons, and respirable dust.

Though limited by factors typical of cohort mortality studies, such as uncertainty in exposure assessments and lack of information on lifestyle factors, this study had strong statistical power and the findings suggest that despite ongoing efforts to reduce diesel engine emissions, diesel exhaust exposure remains a problem.

"Certainly, many workers around the world, in mining and in other industries and jobs, continue to be exposed to REC at levels similar to those observed in this study; in addition, environmental exposures have been shown to reach the levels seen for average REC intensity in surface workers in this study," the investigators concluded.

The findings are bolstered by those from the companion nested case-control study, which also evaluated the relationship between diesel exhaust exposure and lung cancer mortality, but which included adjustment for smoking and other established and hypothesized potential confounders.

For this companion study, Debra T. Silverman, Sc.D., of the National Cancer Institute, Bethesda, Md., and her colleagues compared 198 lung cancer death cases and 562 incidence density–sampled control subjects.

After adjustment for smoking, history of employment in high-risk occupations for lung cancer, and a history of respiratory disease, they also found statistically significant increasing trends in lung cancer risk with increasing exposure (J. Natl. Cancer Inst. 2012;104:1-14 [doi:10.1093/jnci/djs034]).

"Our findings are important not only for miners but also for the 1.4 million American workers and the 3 million European workers exposed to diesel exhaust and for urban populations worldwide," the investigators said.

Citing Los Angeles; the Bronx borough of New York City; Mexico City; Estarreja, Portugal; and nine urban centers in China, they noted that some of the higher-average elemental carbon levels reported in major cities represent potential lifetime exposures that approximate the cumulative exposures experienced by underground miners with low exposures in this study.

"Because such workers had at least a 50% increased lung cancer risk, our results suggest that the high air concentrations of elemental carbon reported in some urban areas may confer increased risk of lung cancer. Thus, if the diesel exhaust/lung cancer relation is causal, the public health burden of the carcinogenicity of inhaled diesel exhaust in workers and in populations of urban areas with high levels of diesel exposure may be substantial," they concluded.

The Diesel Exhaust in Miners Study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. The authors had no disclosures to report.

Exposure to diesel exhaust increases the risk of developing and dying from lung cancer, according to the results of a large cohort mortality study in more than 12,000 exposed workers and a related nested case-control study.

The Diesel Exhaust in Miners Study confirms prior studies demonstrating a possible causal relationship between diesel exhaust exposure and lung cancer, and suggests that this association represents an important public health burden in urban areas worldwide.

Both studies were published online March 5 in the Journal of the National Cancer Institute.

In the main cohort mortality study, the standardized mortality ratio (SMR) of 1.26 for lung cancer among 12,315 exposed workers was significantly greater than were state-based mortality rates, wrote Michael D. Attfield. Ph.D., formerly with the National Institute for Occupational Safety and Health in Morgantown, W.Va., and his colleagues.

Esophageal cancer and pneumoconiosis mortality also were significantly elevated in the exposed workers (SMRs, 1.83 and 12.20, respectively), the researchers found (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs035]).

Outcomes were evaluated in workers exposed to diesel exhaust at eight nonmetal mining facilities in the United States using retrospective quantitative estimates of respirable elemental carbon (REC) exposures as a surrogate for diesel exhaust exposure. The data covered the periods from the introduction (between 1947 and 1967) of diesel-powered equipment to 1997.

A dose-response relationship between exposure and lung cancer mortality was not apparent in the overall cohort, but clear evidence of such a relationship emerged after the investigators divided the population, comparing those who had worked underground at some point (ever-underground) with surface workers.

"In contrast to the complete cohort, hazard ratios that increased with level of exposure were seen for ever-underground workers using quartiles of REC exposure. Using the expanded exposure categories, hazard ratios for 15-year lagged cumulative REC exposure rose with increasing exposure, the trend being more pronounced when workers with shorter tenures were excluded," the investigators said.

As for the surface-only workers, no clear exposure-response trend was seen in the quartile analysis, but there was evidence of an increasing trend in risk with increasing exposure, they said.

The overall findings were "essentially unchanged" after the researchers controlled for cumulative exposures to silica, asbestos, nondiesel exhaust polycyclic aromatic hydrocarbons, and respirable dust.

Though limited by factors typical of cohort mortality studies, such as uncertainty in exposure assessments and lack of information on lifestyle factors, this study had strong statistical power and the findings suggest that despite ongoing efforts to reduce diesel engine emissions, diesel exhaust exposure remains a problem.

"Certainly, many workers around the world, in mining and in other industries and jobs, continue to be exposed to REC at levels similar to those observed in this study; in addition, environmental exposures have been shown to reach the levels seen for average REC intensity in surface workers in this study," the investigators concluded.

The findings are bolstered by those from the companion nested case-control study, which also evaluated the relationship between diesel exhaust exposure and lung cancer mortality, but which included adjustment for smoking and other established and hypothesized potential confounders.

For this companion study, Debra T. Silverman, Sc.D., of the National Cancer Institute, Bethesda, Md., and her colleagues compared 198 lung cancer death cases and 562 incidence density–sampled control subjects.

After adjustment for smoking, history of employment in high-risk occupations for lung cancer, and a history of respiratory disease, they also found statistically significant increasing trends in lung cancer risk with increasing exposure (J. Natl. Cancer Inst. 2012;104:1-14 [doi:10.1093/jnci/djs034]).

"Our findings are important not only for miners but also for the 1.4 million American workers and the 3 million European workers exposed to diesel exhaust and for urban populations worldwide," the investigators said.

Citing Los Angeles; the Bronx borough of New York City; Mexico City; Estarreja, Portugal; and nine urban centers in China, they noted that some of the higher-average elemental carbon levels reported in major cities represent potential lifetime exposures that approximate the cumulative exposures experienced by underground miners with low exposures in this study.

"Because such workers had at least a 50% increased lung cancer risk, our results suggest that the high air concentrations of elemental carbon reported in some urban areas may confer increased risk of lung cancer. Thus, if the diesel exhaust/lung cancer relation is causal, the public health burden of the carcinogenicity of inhaled diesel exhaust in workers and in populations of urban areas with high levels of diesel exposure may be substantial," they concluded.

The Diesel Exhaust in Miners Study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. The authors had no disclosures to report.

Exposure to diesel exhaust increases the risk of developing and dying from lung cancer, according to the results of a large cohort mortality study in more than 12,000 exposed workers and a related nested case-control study.

The Diesel Exhaust in Miners Study confirms prior studies demonstrating a possible causal relationship between diesel exhaust exposure and lung cancer, and suggests that this association represents an important public health burden in urban areas worldwide.

Both studies were published online March 5 in the Journal of the National Cancer Institute.

In the main cohort mortality study, the standardized mortality ratio (SMR) of 1.26 for lung cancer among 12,315 exposed workers was significantly greater than were state-based mortality rates, wrote Michael D. Attfield. Ph.D., formerly with the National Institute for Occupational Safety and Health in Morgantown, W.Va., and his colleagues.

Esophageal cancer and pneumoconiosis mortality also were significantly elevated in the exposed workers (SMRs, 1.83 and 12.20, respectively), the researchers found (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs035]).

Outcomes were evaluated in workers exposed to diesel exhaust at eight nonmetal mining facilities in the United States using retrospective quantitative estimates of respirable elemental carbon (REC) exposures as a surrogate for diesel exhaust exposure. The data covered the periods from the introduction (between 1947 and 1967) of diesel-powered equipment to 1997.

A dose-response relationship between exposure and lung cancer mortality was not apparent in the overall cohort, but clear evidence of such a relationship emerged after the investigators divided the population, comparing those who had worked underground at some point (ever-underground) with surface workers.

"In contrast to the complete cohort, hazard ratios that increased with level of exposure were seen for ever-underground workers using quartiles of REC exposure. Using the expanded exposure categories, hazard ratios for 15-year lagged cumulative REC exposure rose with increasing exposure, the trend being more pronounced when workers with shorter tenures were excluded," the investigators said.

As for the surface-only workers, no clear exposure-response trend was seen in the quartile analysis, but there was evidence of an increasing trend in risk with increasing exposure, they said.

The overall findings were "essentially unchanged" after the researchers controlled for cumulative exposures to silica, asbestos, nondiesel exhaust polycyclic aromatic hydrocarbons, and respirable dust.

Though limited by factors typical of cohort mortality studies, such as uncertainty in exposure assessments and lack of information on lifestyle factors, this study had strong statistical power and the findings suggest that despite ongoing efforts to reduce diesel engine emissions, diesel exhaust exposure remains a problem.

"Certainly, many workers around the world, in mining and in other industries and jobs, continue to be exposed to REC at levels similar to those observed in this study; in addition, environmental exposures have been shown to reach the levels seen for average REC intensity in surface workers in this study," the investigators concluded.

The findings are bolstered by those from the companion nested case-control study, which also evaluated the relationship between diesel exhaust exposure and lung cancer mortality, but which included adjustment for smoking and other established and hypothesized potential confounders.

For this companion study, Debra T. Silverman, Sc.D., of the National Cancer Institute, Bethesda, Md., and her colleagues compared 198 lung cancer death cases and 562 incidence density–sampled control subjects.

After adjustment for smoking, history of employment in high-risk occupations for lung cancer, and a history of respiratory disease, they also found statistically significant increasing trends in lung cancer risk with increasing exposure (J. Natl. Cancer Inst. 2012;104:1-14 [doi:10.1093/jnci/djs034]).

"Our findings are important not only for miners but also for the 1.4 million American workers and the 3 million European workers exposed to diesel exhaust and for urban populations worldwide," the investigators said.

Citing Los Angeles; the Bronx borough of New York City; Mexico City; Estarreja, Portugal; and nine urban centers in China, they noted that some of the higher-average elemental carbon levels reported in major cities represent potential lifetime exposures that approximate the cumulative exposures experienced by underground miners with low exposures in this study.

"Because such workers had at least a 50% increased lung cancer risk, our results suggest that the high air concentrations of elemental carbon reported in some urban areas may confer increased risk of lung cancer. Thus, if the diesel exhaust/lung cancer relation is causal, the public health burden of the carcinogenicity of inhaled diesel exhaust in workers and in populations of urban areas with high levels of diesel exposure may be substantial," they concluded.

The Diesel Exhaust in Miners Study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. The authors had no disclosures to report.

ORLANDO – Researchers have identified risk groups of common perioperative conditions that indicate an increased risk for venous thrombotic events during arterial reconstruction procedures in an analysis of a large administrative database.

The findings could lead to more aggressive venous thrombotic event (VTE) prophylaxis strategies for patients with those "risk families," Dr. Leila Mureebe said at the annual meeting of the American Venous Forum.

Infectious and pulmonary risk families were more commonly associated with VTE. Urinary and intestinal risk families were associated with a lower – although still important – risk of VTEs, said Dr. Mureebe, a vascular surgeon at Duke University in Durham, N.C.

Rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after common vascular procedures are poorly defined. However, determining the true incidence and/or prevalence would be impractical, she noted.

The researchers used administrative data from the National Inpatient Sample (NIS) to identify patients at increased risk of VTE by identifying associated pre- and postoperative factors. The NIS captures discharges by procedure, and is designed to approximate a 20% sample of U.S. community hospitals. All discharges from sampled hospitals are included in the NIS database, which contains clinical and resource-use information (typically included in a discharge abstract).

This study included all discharges during 2000-2008 with primary arterial operations (abdominal aortic aneurysm [open], aortobifemoral bypass, carotid endarterectomy, and infrainguinal bypass). Procedure codes were crossed by diagnosis code for DVT and PE diagnoses. Next the researchers subselected the population that was associated with VTE, including VTE discharges.

The incidence of VTE was 0.34% of 73,545 patients undergoing abdominal aortic aneurysm repair, 0.06% of 372,465 patients undergoing carotid endarterectomy, 0.27% of 50,415 patients undergoing aortobifemoral bypass, and 0.31% of 253,234 patients undergoing bypass graft.

"We then created risk families to capture the relatively common perioperative events," said Dr. Mureebe. The risk families included intestinal (ileus, small-bowel obstruction), pulmonary (aspiration, bronchitis, pneumonia, lobar pneumonia), urinary complications (urinary tract infection not otherwise specified, indwelling urinary catheter), infectious complications (postoperative infection, postoperative abscess, intra-abdominal infection, stitch abscess, subabscess, wound complications, septicemia, infection due to vascular device, and systemic inflammatory response syndrome), and cardiac (acute myocardial infarction, acute coronary occlusion without MI).

Potential confounders included age at admission, sex, a history of DVT/PE, and a history of a coagulopathy (clotting defect, thrombocytosis, heparin-induced thrombocytopenia, antithrombin deficiency, and mutations [factor V Leiden, prothrombin gene]). Logistic regression was used to assess the association between VTE and risk families. The model was adjusted for age and sex.

In all, 755,536 weighted procedures were identified. VTEs were found in 1,445 diagnoses, for an overall prevalence of 0.19%. "Interestingly, each family of complications was associated with a different risk of VTE," said Dr. Mureebe. The risk of intestinal family complications was 0.62%. Pulmonary, urinary, and infectious family risk rates were 1.2%, 0.66%, and 1.46%, respectively. "Cardiac fell out of all analyses and was not associated – at least in this dataset – with the development of VTEs."

Confounders were more strongly associated with VTEs, Dr. Mureebe noted. A history of VTE was associated with a 2.2% increased risk, and a history of coagulopathy was associated with a 1.68% increased risk.

"So, in addition to discrete risk families having increased risk, there’s also a different profile dependent upon the actual surgical procedure."

For example, in carotid endarterectomy – which is associated with an overall low risk of VTEs – "we really see a large contribution from these potential risk families," she said.

Dr. Mureebe did not report whether she had any relevant financial disclosures.

ORLANDO – Researchers have identified risk groups of common perioperative conditions that indicate an increased risk for venous thrombotic events during arterial reconstruction procedures in an analysis of a large administrative database.

The findings could lead to more aggressive venous thrombotic event (VTE) prophylaxis strategies for patients with those "risk families," Dr. Leila Mureebe said at the annual meeting of the American Venous Forum.

Infectious and pulmonary risk families were more commonly associated with VTE. Urinary and intestinal risk families were associated with a lower – although still important – risk of VTEs, said Dr. Mureebe, a vascular surgeon at Duke University in Durham, N.C.

Rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after common vascular procedures are poorly defined. However, determining the true incidence and/or prevalence would be impractical, she noted.

The researchers used administrative data from the National Inpatient Sample (NIS) to identify patients at increased risk of VTE by identifying associated pre- and postoperative factors. The NIS captures discharges by procedure, and is designed to approximate a 20% sample of U.S. community hospitals. All discharges from sampled hospitals are included in the NIS database, which contains clinical and resource-use information (typically included in a discharge abstract).

This study included all discharges during 2000-2008 with primary arterial operations (abdominal aortic aneurysm [open], aortobifemoral bypass, carotid endarterectomy, and infrainguinal bypass). Procedure codes were crossed by diagnosis code for DVT and PE diagnoses. Next the researchers subselected the population that was associated with VTE, including VTE discharges.

The incidence of VTE was 0.34% of 73,545 patients undergoing abdominal aortic aneurysm repair, 0.06% of 372,465 patients undergoing carotid endarterectomy, 0.27% of 50,415 patients undergoing aortobifemoral bypass, and 0.31% of 253,234 patients undergoing bypass graft.

"We then created risk families to capture the relatively common perioperative events," said Dr. Mureebe. The risk families included intestinal (ileus, small-bowel obstruction), pulmonary (aspiration, bronchitis, pneumonia, lobar pneumonia), urinary complications (urinary tract infection not otherwise specified, indwelling urinary catheter), infectious complications (postoperative infection, postoperative abscess, intra-abdominal infection, stitch abscess, subabscess, wound complications, septicemia, infection due to vascular device, and systemic inflammatory response syndrome), and cardiac (acute myocardial infarction, acute coronary occlusion without MI).

Potential confounders included age at admission, sex, a history of DVT/PE, and a history of a coagulopathy (clotting defect, thrombocytosis, heparin-induced thrombocytopenia, antithrombin deficiency, and mutations [factor V Leiden, prothrombin gene]). Logistic regression was used to assess the association between VTE and risk families. The model was adjusted for age and sex.

In all, 755,536 weighted procedures were identified. VTEs were found in 1,445 diagnoses, for an overall prevalence of 0.19%. "Interestingly, each family of complications was associated with a different risk of VTE," said Dr. Mureebe. The risk of intestinal family complications was 0.62%. Pulmonary, urinary, and infectious family risk rates were 1.2%, 0.66%, and 1.46%, respectively. "Cardiac fell out of all analyses and was not associated – at least in this dataset – with the development of VTEs."

Confounders were more strongly associated with VTEs, Dr. Mureebe noted. A history of VTE was associated with a 2.2% increased risk, and a history of coagulopathy was associated with a 1.68% increased risk.

"So, in addition to discrete risk families having increased risk, there’s also a different profile dependent upon the actual surgical procedure."

For example, in carotid endarterectomy – which is associated with an overall low risk of VTEs – "we really see a large contribution from these potential risk families," she said.

Dr. Mureebe did not report whether she had any relevant financial disclosures.

ORLANDO – Researchers have identified risk groups of common perioperative conditions that indicate an increased risk for venous thrombotic events during arterial reconstruction procedures in an analysis of a large administrative database.

The findings could lead to more aggressive venous thrombotic event (VTE) prophylaxis strategies for patients with those "risk families," Dr. Leila Mureebe said at the annual meeting of the American Venous Forum.

Infectious and pulmonary risk families were more commonly associated with VTE. Urinary and intestinal risk families were associated with a lower – although still important – risk of VTEs, said Dr. Mureebe, a vascular surgeon at Duke University in Durham, N.C.

Rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after common vascular procedures are poorly defined. However, determining the true incidence and/or prevalence would be impractical, she noted.

The researchers used administrative data from the National Inpatient Sample (NIS) to identify patients at increased risk of VTE by identifying associated pre- and postoperative factors. The NIS captures discharges by procedure, and is designed to approximate a 20% sample of U.S. community hospitals. All discharges from sampled hospitals are included in the NIS database, which contains clinical and resource-use information (typically included in a discharge abstract).

This study included all discharges during 2000-2008 with primary arterial operations (abdominal aortic aneurysm [open], aortobifemoral bypass, carotid endarterectomy, and infrainguinal bypass). Procedure codes were crossed by diagnosis code for DVT and PE diagnoses. Next the researchers subselected the population that was associated with VTE, including VTE discharges.

The incidence of VTE was 0.34% of 73,545 patients undergoing abdominal aortic aneurysm repair, 0.06% of 372,465 patients undergoing carotid endarterectomy, 0.27% of 50,415 patients undergoing aortobifemoral bypass, and 0.31% of 253,234 patients undergoing bypass graft.

"We then created risk families to capture the relatively common perioperative events," said Dr. Mureebe. The risk families included intestinal (ileus, small-bowel obstruction), pulmonary (aspiration, bronchitis, pneumonia, lobar pneumonia), urinary complications (urinary tract infection not otherwise specified, indwelling urinary catheter), infectious complications (postoperative infection, postoperative abscess, intra-abdominal infection, stitch abscess, subabscess, wound complications, septicemia, infection due to vascular device, and systemic inflammatory response syndrome), and cardiac (acute myocardial infarction, acute coronary occlusion without MI).

Potential confounders included age at admission, sex, a history of DVT/PE, and a history of a coagulopathy (clotting defect, thrombocytosis, heparin-induced thrombocytopenia, antithrombin deficiency, and mutations [factor V Leiden, prothrombin gene]). Logistic regression was used to assess the association between VTE and risk families. The model was adjusted for age and sex.

In all, 755,536 weighted procedures were identified. VTEs were found in 1,445 diagnoses, for an overall prevalence of 0.19%. "Interestingly, each family of complications was associated with a different risk of VTE," said Dr. Mureebe. The risk of intestinal family complications was 0.62%. Pulmonary, urinary, and infectious family risk rates were 1.2%, 0.66%, and 1.46%, respectively. "Cardiac fell out of all analyses and was not associated – at least in this dataset – with the development of VTEs."

Confounders were more strongly associated with VTEs, Dr. Mureebe noted. A history of VTE was associated with a 2.2% increased risk, and a history of coagulopathy was associated with a 1.68% increased risk.

"So, in addition to discrete risk families having increased risk, there’s also a different profile dependent upon the actual surgical procedure."

For example, in carotid endarterectomy – which is associated with an overall low risk of VTEs – "we really see a large contribution from these potential risk families," she said.

Dr. Mureebe did not report whether she had any relevant financial disclosures.