HIV update 2002: Delaying treatment to curb rising resistance

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Emphysema in nonsmokers: Alpha 1-antitrypsin deficiency and other causes

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Lumbar canal stenosis: Start with nonsurgical therapy

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A 52-year-old man with sudden onset of a facial rash

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How effective are nasal steroids combined with nonsedating antihistamines for seasonal allergic rhinitis?

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How effective are nasal steroids combined with nonsedating antihistamines for seasonal allergic rhinitis?
EVIDENCE-BASED ANSWER

For treating seasonal allergic rhinitis, inhaled nasal corticosteroids are superior to nonsedating antihistamines (Grade of recommendation: A, based on a large meta-analysis of randomized controlled trials [RCTs]). Combining nasal steroids and nonsedating antihistamines yields no additional benefits (Grade of recommendation: A, based on several RCTs). Unless patient preference limits their use, nasal steroids should be first-line therapy.

 

Evidence summary

A meta-analysis of 16 RCTs compared the efficacy of intranasal steroids and oral antihistamines for alleviating nasal, eye, and global allergy symptoms.1 Intranasal steroids were superior to oral antihistamines for all patient-oriented nasal symptom and global symptom ratings. Eye symptom scores and adverse events were similar in each treatment group.

Several large RCTs have addressed whether combining the 2 classes of drugs would achieve greater symptom control. Only 1 study2 found combination therapy to be superior. This RCT compared beclomethasone dipropionate with loratadine or placebo daily in 154 patients.2 Total symptom scores were better for the combination group mainly due to improved relief from ocular symptoms.

Fluticasone propionate aqueous nasal spray (FPANS) was evaluated alone and in combination with cetirizine in a multicenter double-blind study of 454 patients.3 The mean symptom scores for nasal and eye symptoms were not significantly different between the 2 groups. A more recent RCT had similar results when comparing FPANS with loratadine and with combined therapy.4 This double-blinded placebo-controlled trial, which included 600 patients, measured patient- and clinician-rated total symptom scores, individual nasal symptom scores, and overall evaluations after 7 and 14 days of therapy. Although the symptom scores for the FPANS group were significantly lower than those in the loratadine and placebo groups, no significant difference in scores was found between the FPANS and combined groups. The results were the same for the quality-of-life questionnaire scores. In an RCT of 106 patients, budesonide nasal spray’s efficacy was tested against terfenadine alone and in combination; the nasal steroid alone was more effective than the histamine.5 Combining the 2 drugs yielded no significant improvements.

The newer nasal steroids such as fluticasone may be more effective because of their stronger affinities to glucocorticoid receptors, but no clinical evidence confirms this hypothesis.6

TABLE
Intranasal steroids for treating allergic rhinitis

DrugUsual adult dosagesCost per month*
Beclomethasone dipropionate
  Beconase AQ2 sprays/nostril qd$44
  Vancenase AQ2 sprays/nostril qd$40
Budesonide
  Rhinocort AQ2 sprays/nostril bid$48
Flunisolide
  Nasarel2 sprays/nostril bid$44
  Nasalide2 sprays/nostril bid$46
Fluticasone propionate
  Flonase2 sprays/nostril qd$53
Mometasone furoate
  Nasonex2 sprays/nostril qd$56
Triamcinolone acetonide
  Nasacort AQ2 sprays/nostril qd$56
bid, twice a day; qd, every day.
*Red Book. Medical Economics Data, 2001.

Recommendations from others

The Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology recommends second-generation oral antihistamines for first-line therapy, but notes that nasal steroids are the most effective medication class for controlling allergy symptoms.7 The task force states that combination drug therapy may be tried. A monograph from the American Academy of Family Physicians notes the lack of consensus guidelines for first-line therapy and recommends that treatment be individualized.8 It states that combination therapy may be tried if monotherapy fails.

Clinical Commentaries by Tsveti Markova, MD, and John W. Tipton, MD, at http://www.FPIN.org.

References

1. Weiner JM, Abramson MJ, Puy RM. Br Med J 1998;317:1624-9.

2. Drouin MA, Yang WH, Horak F, et al. Allergy 1992;12(suppl):173.-

3. Benincasa C, Lloyd RS. Drug Invest 1994;8:225-33.

4. Ratner PH, Van Bavel JH, Martin BG, et al. J Fam Pract 1998;47:118-25.

5. Simpson RJ. Ann Allergy 1994;73:497-502.

6. Lumry J. Allergy Clin Immunol 2000; 105:394. J Allergy Clin Immunol 1999;104(4 Pt 1):S150-8.

7. Dykewicz M, Fineman S. Ann Allergy Asthma Immunol 1998;81:463-518.

8. Diagnosis and Management of Allergic Rhinitis. American Family Physician Monograph no. 3; 2001.

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EVIDENCE-BASED ANSWER

For treating seasonal allergic rhinitis, inhaled nasal corticosteroids are superior to nonsedating antihistamines (Grade of recommendation: A, based on a large meta-analysis of randomized controlled trials [RCTs]). Combining nasal steroids and nonsedating antihistamines yields no additional benefits (Grade of recommendation: A, based on several RCTs). Unless patient preference limits their use, nasal steroids should be first-line therapy.

 

Evidence summary

A meta-analysis of 16 RCTs compared the efficacy of intranasal steroids and oral antihistamines for alleviating nasal, eye, and global allergy symptoms.1 Intranasal steroids were superior to oral antihistamines for all patient-oriented nasal symptom and global symptom ratings. Eye symptom scores and adverse events were similar in each treatment group.

Several large RCTs have addressed whether combining the 2 classes of drugs would achieve greater symptom control. Only 1 study2 found combination therapy to be superior. This RCT compared beclomethasone dipropionate with loratadine or placebo daily in 154 patients.2 Total symptom scores were better for the combination group mainly due to improved relief from ocular symptoms.

Fluticasone propionate aqueous nasal spray (FPANS) was evaluated alone and in combination with cetirizine in a multicenter double-blind study of 454 patients.3 The mean symptom scores for nasal and eye symptoms were not significantly different between the 2 groups. A more recent RCT had similar results when comparing FPANS with loratadine and with combined therapy.4 This double-blinded placebo-controlled trial, which included 600 patients, measured patient- and clinician-rated total symptom scores, individual nasal symptom scores, and overall evaluations after 7 and 14 days of therapy. Although the symptom scores for the FPANS group were significantly lower than those in the loratadine and placebo groups, no significant difference in scores was found between the FPANS and combined groups. The results were the same for the quality-of-life questionnaire scores. In an RCT of 106 patients, budesonide nasal spray’s efficacy was tested against terfenadine alone and in combination; the nasal steroid alone was more effective than the histamine.5 Combining the 2 drugs yielded no significant improvements.

The newer nasal steroids such as fluticasone may be more effective because of their stronger affinities to glucocorticoid receptors, but no clinical evidence confirms this hypothesis.6

TABLE
Intranasal steroids for treating allergic rhinitis

DrugUsual adult dosagesCost per month*
Beclomethasone dipropionate
  Beconase AQ2 sprays/nostril qd$44
  Vancenase AQ2 sprays/nostril qd$40
Budesonide
  Rhinocort AQ2 sprays/nostril bid$48
Flunisolide
  Nasarel2 sprays/nostril bid$44
  Nasalide2 sprays/nostril bid$46
Fluticasone propionate
  Flonase2 sprays/nostril qd$53
Mometasone furoate
  Nasonex2 sprays/nostril qd$56
Triamcinolone acetonide
  Nasacort AQ2 sprays/nostril qd$56
bid, twice a day; qd, every day.
*Red Book. Medical Economics Data, 2001.

Recommendations from others

The Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology recommends second-generation oral antihistamines for first-line therapy, but notes that nasal steroids are the most effective medication class for controlling allergy symptoms.7 The task force states that combination drug therapy may be tried. A monograph from the American Academy of Family Physicians notes the lack of consensus guidelines for first-line therapy and recommends that treatment be individualized.8 It states that combination therapy may be tried if monotherapy fails.

Clinical Commentaries by Tsveti Markova, MD, and John W. Tipton, MD, at http://www.FPIN.org.

EVIDENCE-BASED ANSWER

For treating seasonal allergic rhinitis, inhaled nasal corticosteroids are superior to nonsedating antihistamines (Grade of recommendation: A, based on a large meta-analysis of randomized controlled trials [RCTs]). Combining nasal steroids and nonsedating antihistamines yields no additional benefits (Grade of recommendation: A, based on several RCTs). Unless patient preference limits their use, nasal steroids should be first-line therapy.

 

Evidence summary

A meta-analysis of 16 RCTs compared the efficacy of intranasal steroids and oral antihistamines for alleviating nasal, eye, and global allergy symptoms.1 Intranasal steroids were superior to oral antihistamines for all patient-oriented nasal symptom and global symptom ratings. Eye symptom scores and adverse events were similar in each treatment group.

Several large RCTs have addressed whether combining the 2 classes of drugs would achieve greater symptom control. Only 1 study2 found combination therapy to be superior. This RCT compared beclomethasone dipropionate with loratadine or placebo daily in 154 patients.2 Total symptom scores were better for the combination group mainly due to improved relief from ocular symptoms.

Fluticasone propionate aqueous nasal spray (FPANS) was evaluated alone and in combination with cetirizine in a multicenter double-blind study of 454 patients.3 The mean symptom scores for nasal and eye symptoms were not significantly different between the 2 groups. A more recent RCT had similar results when comparing FPANS with loratadine and with combined therapy.4 This double-blinded placebo-controlled trial, which included 600 patients, measured patient- and clinician-rated total symptom scores, individual nasal symptom scores, and overall evaluations after 7 and 14 days of therapy. Although the symptom scores for the FPANS group were significantly lower than those in the loratadine and placebo groups, no significant difference in scores was found between the FPANS and combined groups. The results were the same for the quality-of-life questionnaire scores. In an RCT of 106 patients, budesonide nasal spray’s efficacy was tested against terfenadine alone and in combination; the nasal steroid alone was more effective than the histamine.5 Combining the 2 drugs yielded no significant improvements.

The newer nasal steroids such as fluticasone may be more effective because of their stronger affinities to glucocorticoid receptors, but no clinical evidence confirms this hypothesis.6

TABLE
Intranasal steroids for treating allergic rhinitis

DrugUsual adult dosagesCost per month*
Beclomethasone dipropionate
  Beconase AQ2 sprays/nostril qd$44
  Vancenase AQ2 sprays/nostril qd$40
Budesonide
  Rhinocort AQ2 sprays/nostril bid$48
Flunisolide
  Nasarel2 sprays/nostril bid$44
  Nasalide2 sprays/nostril bid$46
Fluticasone propionate
  Flonase2 sprays/nostril qd$53
Mometasone furoate
  Nasonex2 sprays/nostril qd$56
Triamcinolone acetonide
  Nasacort AQ2 sprays/nostril qd$56
bid, twice a day; qd, every day.
*Red Book. Medical Economics Data, 2001.

Recommendations from others

The Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology recommends second-generation oral antihistamines for first-line therapy, but notes that nasal steroids are the most effective medication class for controlling allergy symptoms.7 The task force states that combination drug therapy may be tried. A monograph from the American Academy of Family Physicians notes the lack of consensus guidelines for first-line therapy and recommends that treatment be individualized.8 It states that combination therapy may be tried if monotherapy fails.

Clinical Commentaries by Tsveti Markova, MD, and John W. Tipton, MD, at http://www.FPIN.org.

References

1. Weiner JM, Abramson MJ, Puy RM. Br Med J 1998;317:1624-9.

2. Drouin MA, Yang WH, Horak F, et al. Allergy 1992;12(suppl):173.-

3. Benincasa C, Lloyd RS. Drug Invest 1994;8:225-33.

4. Ratner PH, Van Bavel JH, Martin BG, et al. J Fam Pract 1998;47:118-25.

5. Simpson RJ. Ann Allergy 1994;73:497-502.

6. Lumry J. Allergy Clin Immunol 2000; 105:394. J Allergy Clin Immunol 1999;104(4 Pt 1):S150-8.

7. Dykewicz M, Fineman S. Ann Allergy Asthma Immunol 1998;81:463-518.

8. Diagnosis and Management of Allergic Rhinitis. American Family Physician Monograph no. 3; 2001.

References

1. Weiner JM, Abramson MJ, Puy RM. Br Med J 1998;317:1624-9.

2. Drouin MA, Yang WH, Horak F, et al. Allergy 1992;12(suppl):173.-

3. Benincasa C, Lloyd RS. Drug Invest 1994;8:225-33.

4. Ratner PH, Van Bavel JH, Martin BG, et al. J Fam Pract 1998;47:118-25.

5. Simpson RJ. Ann Allergy 1994;73:497-502.

6. Lumry J. Allergy Clin Immunol 2000; 105:394. J Allergy Clin Immunol 1999;104(4 Pt 1):S150-8.

7. Dykewicz M, Fineman S. Ann Allergy Asthma Immunol 1998;81:463-518.

8. Diagnosis and Management of Allergic Rhinitis. American Family Physician Monograph no. 3; 2001.

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Which is more effective for as-needed treatment of seasonal allergy symptoms: intranasal corticosteroids or oral antihistamines?

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ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study shows that for as-needed treatment of allergic rhinitis, fluticasone propionate appears to be superior to loratadine in both subjective and objective measurements. A double-blind design would have strengthened our confidence in these results. Regular use of intranasal steroids has also been demonstrated to provide better symptom control than antihistamines do. The clinician may consider prescribing as-needed antihistamines or intranasal steroids for first-line treatment of allergic rhinitis.

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Department of Family Practice Thomas Jefferson University Hospital Philadelphia, Pennsylvania
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ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study shows that for as-needed treatment of allergic rhinitis, fluticasone propionate appears to be superior to loratadine in both subjective and objective measurements. A double-blind design would have strengthened our confidence in these results. Regular use of intranasal steroids has also been demonstrated to provide better symptom control than antihistamines do. The clinician may consider prescribing as-needed antihistamines or intranasal steroids for first-line treatment of allergic rhinitis.

ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study shows that for as-needed treatment of allergic rhinitis, fluticasone propionate appears to be superior to loratadine in both subjective and objective measurements. A double-blind design would have strengthened our confidence in these results. Regular use of intranasal steroids has also been demonstrated to provide better symptom control than antihistamines do. The clinician may consider prescribing as-needed antihistamines or intranasal steroids for first-line treatment of allergic rhinitis.

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