It’s in the nose

 

There is a lot more going on in the nose besides air going in and out. The nose is where it all begins for pathogenesis for all respiratory infections. The interplay between the commensal microbes, the potential pathogens, innate immunity, and adaptive immunity is much more complex than was previously understood. So what is new?

In our research on acute otitis media, we swab and wash out noses of children aged 6-36 months to isolate the potential pathogens Streptococcus pneumoniae, nontypeable Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Group A streptococci. We isolate one or more of these bacteria from most of the children even though they are well. We observe perhaps a half-dozen other species of bacteria on the culture plate. Mostly, we isolate S. pneumoniae, nontypeable H. influenza, or M. catarrhalis and alpha-hemolytic streptococci and corynebacterium species.

When the children show symptoms of a viral upper respiratory infection, we wash out their nose with saline and look for the DNA or RNA of possible respiratory viruses. Between half and two-thirds of the time, we detect 1 of the 11 most common respiratory viruses. What is new is that we now know there is a lot more microbial activity than we detect because most of the microbes living in the nose we cannot culture or detect by standard molecular biology methods.

We have recently begun to investigate the other microbiota in the nose and found they are indeed plentiful. In a recent screening of a half-dozen children, we found hundreds of different microbes in their noses, so cultures and standard molecular detection methods were just touching the surface. I was asked recently at a medical conference – the American Academy of Pediatrics– Orange County, California, annual CME course – at which I spoke on this topic what I thought would be the most-important area of research in the next decade. I responded, the microbiome. The microbiome is indeed a hot topic. Research over the last decade suggests that 90% of all diseases can be traced in some way to disturbances in the microbiome. What I mean by microbiome is “the totality of microorganisms and their collective genetic material present in or on the human body.” The term is often used interchangeably with “microbiota,” although the former refers to genes of microbes and the latter refers to the microbes themselves. What I mean by “disturbance” is excessive use of antibiotics.

How many microbes are in the nose? We don’t know. But if the gut is any indication, there are thousands of microbes in the nose because the gut has more than 10,000 different microbes. Recognizing that there are hundreds of microbes in the nose and from time to time children get colonized by potential pathogens that can cause otitis media, sinusitis, or pneumonia, how does pathogenesis get started? It starts with a respiratory virus infection. The bacteria need help from the viruses to cause disease. The viruses cause damage to the epithelial cells of the nose, and this gives the bacteria more places to attach when they divide so the amount of bacteria increases exponentially. As the viruses replicate, they more effectively slow down cilia beating, and the nasal mucus thickens. This, too, helps the bacteria and viruses attach to and penetrate epithelial cells in the nose and increase in density on the surface of the cells and inside the cells. The viruses divert and/or suppress the innate immune system, represented by neutrophils that migrate to the nose and discharge their intracellular contents to turn nasal mucus yellow and green. The viruses even down-modulate the adaptive immune system in clever ways that result in fewer potentially protective cytotoxic lymphocytes that kill viruses making their way to the nose, and fewer T cells that discharge cytokines that promote a necessary inflammatory response to clear both bacteria and viruses from the nose and fewer B cells that become plasma cells and release antibodies into the nose.

When the bacteria with potential to cause diseases reach a “pathogenic threshold,” they move, along with mucus, into the middle ear, the sinuses, or down the throat to the lungs, usually with the accompanying respiratory virus. There pathogenesis continues in the otherwise sterile and protected sanctuary of these interconnected respiratory sites. A few days later, we as clinicians observe the symptoms and signs of otitis media, sinusitis, or pneumonia.

What can we do to help the nose? Mostly, we should do no harm, and that has been our failing for decades since the introduction of antibiotics. The allure of antibiotics is great because they have indeed saved many lives and shortened many illnesses when appropriately used. However, too often clinicians have seen patients with yellow and green nasal mucus (or any increased nasal mucus) and diagnosed “a bacterial infection” and prescribed antibiotics. And too often clinicians have seen patients with an annoying cough (or any cough) and diagnosed “a bacterial chest infection” and prescribed antibiotics. The clinicians thought it was the right thing to do because they wanted to help their patient. And they did not want them to come back in a few days with persistence or worsening of symptoms, or worse, seek care from other health care providers elsewhere. So they gave antibiotics.

Well, the paradigm has changed. It is now clearly known that antibiotics can be harmful mainly by damaging the normal, healthy microbiome. The change in healthy homeostasis of the microbiome wrought by antibiotics is greatest in newborns, especially premature newborns, then next worst for infants, and then next worst for young children. These are the age groups where antibiotics are prescribed most frequently! And everyone needs to stop writing those prescriptions for runny noses, yellow and green mucus in the nose, and coughs. All of us need to prescribe antibiotics only when there is an accurate diagnosis of otitis media or sinusitis or bronchopneumonia or lobar pneumonia. And when we do prescribe the antibiotics ,we need to give them for as short a time as possible. But that is a topic for another column.
 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he has no relevant financial disclosures, and that his research is supported by a grant from the National Institutes of Health National Institute of Deafness and Communication Disorders. Email him at pdnews@frontlinemedcom.com.

 

There is a lot more going on in the nose besides air going in and out. The nose is where it all begins for pathogenesis for all respiratory infections. The interplay between the commensal microbes, the potential pathogens, innate immunity, and adaptive immunity is much more complex than was previously understood. So what is new?

In our research on acute otitis media, we swab and wash out noses of children aged 6-36 months to isolate the potential pathogens Streptococcus pneumoniae, nontypeable Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Group A streptococci. We isolate one or more of these bacteria from most of the children even though they are well. We observe perhaps a half-dozen other species of bacteria on the culture plate. Mostly, we isolate S. pneumoniae, nontypeable H. influenza, or M. catarrhalis and alpha-hemolytic streptococci and corynebacterium species.

When the children show symptoms of a viral upper respiratory infection, we wash out their nose with saline and look for the DNA or RNA of possible respiratory viruses. Between half and two-thirds of the time, we detect 1 of the 11 most common respiratory viruses. What is new is that we now know there is a lot more microbial activity than we detect because most of the microbes living in the nose we cannot culture or detect by standard molecular biology methods.

We have recently begun to investigate the other microbiota in the nose and found they are indeed plentiful. In a recent screening of a half-dozen children, we found hundreds of different microbes in their noses, so cultures and standard molecular detection methods were just touching the surface. I was asked recently at a medical conference – the American Academy of Pediatrics– Orange County, California, annual CME course – at which I spoke on this topic what I thought would be the most-important area of research in the next decade. I responded, the microbiome. The microbiome is indeed a hot topic. Research over the last decade suggests that 90% of all diseases can be traced in some way to disturbances in the microbiome. What I mean by microbiome is “the totality of microorganisms and their collective genetic material present in or on the human body.” The term is often used interchangeably with “microbiota,” although the former refers to genes of microbes and the latter refers to the microbes themselves. What I mean by “disturbance” is excessive use of antibiotics.

How many microbes are in the nose? We don’t know. But if the gut is any indication, there are thousands of microbes in the nose because the gut has more than 10,000 different microbes. Recognizing that there are hundreds of microbes in the nose and from time to time children get colonized by potential pathogens that can cause otitis media, sinusitis, or pneumonia, how does pathogenesis get started? It starts with a respiratory virus infection. The bacteria need help from the viruses to cause disease. The viruses cause damage to the epithelial cells of the nose, and this gives the bacteria more places to attach when they divide so the amount of bacteria increases exponentially. As the viruses replicate, they more effectively slow down cilia beating, and the nasal mucus thickens. This, too, helps the bacteria and viruses attach to and penetrate epithelial cells in the nose and increase in density on the surface of the cells and inside the cells. The viruses divert and/or suppress the innate immune system, represented by neutrophils that migrate to the nose and discharge their intracellular contents to turn nasal mucus yellow and green. The viruses even down-modulate the adaptive immune system in clever ways that result in fewer potentially protective cytotoxic lymphocytes that kill viruses making their way to the nose, and fewer T cells that discharge cytokines that promote a necessary inflammatory response to clear both bacteria and viruses from the nose and fewer B cells that become plasma cells and release antibodies into the nose.

When the bacteria with potential to cause diseases reach a “pathogenic threshold,” they move, along with mucus, into the middle ear, the sinuses, or down the throat to the lungs, usually with the accompanying respiratory virus. There pathogenesis continues in the otherwise sterile and protected sanctuary of these interconnected respiratory sites. A few days later, we as clinicians observe the symptoms and signs of otitis media, sinusitis, or pneumonia.

What can we do to help the nose? Mostly, we should do no harm, and that has been our failing for decades since the introduction of antibiotics. The allure of antibiotics is great because they have indeed saved many lives and shortened many illnesses when appropriately used. However, too often clinicians have seen patients with yellow and green nasal mucus (or any increased nasal mucus) and diagnosed “a bacterial infection” and prescribed antibiotics. And too often clinicians have seen patients with an annoying cough (or any cough) and diagnosed “a bacterial chest infection” and prescribed antibiotics. The clinicians thought it was the right thing to do because they wanted to help their patient. And they did not want them to come back in a few days with persistence or worsening of symptoms, or worse, seek care from other health care providers elsewhere. So they gave antibiotics.

Well, the paradigm has changed. It is now clearly known that antibiotics can be harmful mainly by damaging the normal, healthy microbiome. The change in healthy homeostasis of the microbiome wrought by antibiotics is greatest in newborns, especially premature newborns, then next worst for infants, and then next worst for young children. These are the age groups where antibiotics are prescribed most frequently! And everyone needs to stop writing those prescriptions for runny noses, yellow and green mucus in the nose, and coughs. All of us need to prescribe antibiotics only when there is an accurate diagnosis of otitis media or sinusitis or bronchopneumonia or lobar pneumonia. And when we do prescribe the antibiotics ,we need to give them for as short a time as possible. But that is a topic for another column.
 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he has no relevant financial disclosures, and that his research is supported by a grant from the National Institutes of Health National Institute of Deafness and Communication Disorders. Email him at pdnews@frontlinemedcom.com.

 

There is a lot more going on in the nose besides air going in and out. The nose is where it all begins for pathogenesis for all respiratory infections. The interplay between the commensal microbes, the potential pathogens, innate immunity, and adaptive immunity is much more complex than was previously understood. So what is new?

In our research on acute otitis media, we swab and wash out noses of children aged 6-36 months to isolate the potential pathogens Streptococcus pneumoniae, nontypeable Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Group A streptococci. We isolate one or more of these bacteria from most of the children even though they are well. We observe perhaps a half-dozen other species of bacteria on the culture plate. Mostly, we isolate S. pneumoniae, nontypeable H. influenza, or M. catarrhalis and alpha-hemolytic streptococci and corynebacterium species.

When the children show symptoms of a viral upper respiratory infection, we wash out their nose with saline and look for the DNA or RNA of possible respiratory viruses. Between half and two-thirds of the time, we detect 1 of the 11 most common respiratory viruses. What is new is that we now know there is a lot more microbial activity than we detect because most of the microbes living in the nose we cannot culture or detect by standard molecular biology methods.

We have recently begun to investigate the other microbiota in the nose and found they are indeed plentiful. In a recent screening of a half-dozen children, we found hundreds of different microbes in their noses, so cultures and standard molecular detection methods were just touching the surface. I was asked recently at a medical conference – the American Academy of Pediatrics– Orange County, California, annual CME course – at which I spoke on this topic what I thought would be the most-important area of research in the next decade. I responded, the microbiome. The microbiome is indeed a hot topic. Research over the last decade suggests that 90% of all diseases can be traced in some way to disturbances in the microbiome. What I mean by microbiome is “the totality of microorganisms and their collective genetic material present in or on the human body.” The term is often used interchangeably with “microbiota,” although the former refers to genes of microbes and the latter refers to the microbes themselves. What I mean by “disturbance” is excessive use of antibiotics.

How many microbes are in the nose? We don’t know. But if the gut is any indication, there are thousands of microbes in the nose because the gut has more than 10,000 different microbes. Recognizing that there are hundreds of microbes in the nose and from time to time children get colonized by potential pathogens that can cause otitis media, sinusitis, or pneumonia, how does pathogenesis get started? It starts with a respiratory virus infection. The bacteria need help from the viruses to cause disease. The viruses cause damage to the epithelial cells of the nose, and this gives the bacteria more places to attach when they divide so the amount of bacteria increases exponentially. As the viruses replicate, they more effectively slow down cilia beating, and the nasal mucus thickens. This, too, helps the bacteria and viruses attach to and penetrate epithelial cells in the nose and increase in density on the surface of the cells and inside the cells. The viruses divert and/or suppress the innate immune system, represented by neutrophils that migrate to the nose and discharge their intracellular contents to turn nasal mucus yellow and green. The viruses even down-modulate the adaptive immune system in clever ways that result in fewer potentially protective cytotoxic lymphocytes that kill viruses making their way to the nose, and fewer T cells that discharge cytokines that promote a necessary inflammatory response to clear both bacteria and viruses from the nose and fewer B cells that become plasma cells and release antibodies into the nose.

When the bacteria with potential to cause diseases reach a “pathogenic threshold,” they move, along with mucus, into the middle ear, the sinuses, or down the throat to the lungs, usually with the accompanying respiratory virus. There pathogenesis continues in the otherwise sterile and protected sanctuary of these interconnected respiratory sites. A few days later, we as clinicians observe the symptoms and signs of otitis media, sinusitis, or pneumonia.

What can we do to help the nose? Mostly, we should do no harm, and that has been our failing for decades since the introduction of antibiotics. The allure of antibiotics is great because they have indeed saved many lives and shortened many illnesses when appropriately used. However, too often clinicians have seen patients with yellow and green nasal mucus (or any increased nasal mucus) and diagnosed “a bacterial infection” and prescribed antibiotics. And too often clinicians have seen patients with an annoying cough (or any cough) and diagnosed “a bacterial chest infection” and prescribed antibiotics. The clinicians thought it was the right thing to do because they wanted to help their patient. And they did not want them to come back in a few days with persistence or worsening of symptoms, or worse, seek care from other health care providers elsewhere. So they gave antibiotics.

Well, the paradigm has changed. It is now clearly known that antibiotics can be harmful mainly by damaging the normal, healthy microbiome. The change in healthy homeostasis of the microbiome wrought by antibiotics is greatest in newborns, especially premature newborns, then next worst for infants, and then next worst for young children. These are the age groups where antibiotics are prescribed most frequently! And everyone needs to stop writing those prescriptions for runny noses, yellow and green mucus in the nose, and coughs. All of us need to prescribe antibiotics only when there is an accurate diagnosis of otitis media or sinusitis or bronchopneumonia or lobar pneumonia. And when we do prescribe the antibiotics ,we need to give them for as short a time as possible. But that is a topic for another column.
 

 

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he has no relevant financial disclosures, and that his research is supported by a grant from the National Institutes of Health National Institute of Deafness and Communication Disorders. Email him at pdnews@frontlinemedcom.com.