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Dr. Purvi Parikh: Welcome to this special edition of Allergy Talk from the American College of Allergy, Asthma and Immunology. I am Dr. Purvi Parikh and this is the second episode in a three part series on cough. Diagnosing the Patients Cough. Joining me are Dr. Kevin Murphy, the Director of Clinical Research at Boys Town National Research Hospital in Omaha, Nebraska. He completed a fellowship in Allergy, Asthma, Immunology and Pediatric Pulmonary at National Jewish Hospital. He's a spokesperson for the American College of Allergy, Asthma and Immunology. And Dr. Mandel Sher, Clinical Professor of Medicine and Pediatrics at Morsani College of Medicine at University of Southern Florida in the division of Allergy and Immunology. Dr. Sher is the Head of the Center for Cough in Largo, Florida with large chronic cough population and engaged in clinical investigation in promising and novel cough suppressants and controllers. He is a speaker on local, regional, and national levels on diagnosis and treatment of chronic cough and is also a spokesperson for the American College of Allergy, Asthma and Immunology. Thanks for joining us again, Doctors. So let's get started. Mandel, can you tell us about the diagnostic approach for chronic cough in adults?

Dr. Sher: I thank you. Purvi chronic cough is defined as a cough lasting more than eight weeks, you know, and first and foremost, our clinical obligation is an attempt to identify the cause for that cough, be it from an anatomic problem or some other issue. Maybe they're on an ACE inhibitor, which we are, we know that they're associated with chronic cough. So there's been a common approach to cough over the last decades and the mantra has gone that in a nonsmoker who has a normal chest X Ray, which is extremely important in ruling out particularly malignancies, and not being on an ACE inhibitor, you proceed through an anatomic approach, if you will in trying to find the cause of a cough. And it includes the triad of an upper airway, lower airway and gastroesophogeal contribution, be it acid or non acid. I think we as allergists are highly expert in evaluating and treating upper airway involvement. But the point I'd like to make, and I think for us who are rhinologists as allergists is that cough, as a sole manifestation of upper airway diseases is really uncommon. Upper airway disease almost involves other symptoms, be it mucus or nasal congestion, sinus pressure, so I think we're really good at doing that. Identifying chest disease, it's a little bit more problematic, we're expertise of that as allergists, but cough may be the sole manifestation of a lower respiratory disease, cough, asthma, interstitial pulmonary fibrosis.

Other diagnoses can present with cough but with only a cough and there I think that's where other diagnostic tests are helpful and that I'd like to emphasize the high resolution chest CT scan. Using a high Res chest CT scan earlier when you're not finding a red oval diagnosis I think is extremely important. And then there's the issue of acid, non acid reflux where there's various diagnostic and therapeutic approaches. History is always important and I'd like to emphasize a history of mucus production. Kevin in our last session talked about dry cough and mucus cough as refers to children. I'd like to emphasize that also in adults, looking for objective evidence of mucus is important. If you're making mucus, the odds are you have an anatomic problem causing your cough. But again, patients, coughers have neurosensory hypersensitivity so they complain of post nasal drip, but many times that's a sensation rather than objective mucus production. So it's important to pursue that much further. And furthermore, I think we'll talk a little bit more GERD, but I'd like to hear what Dr. Murphy has to say regarding pediatric patients.

Dr. Murphy: Mandel, I really liked the way you think about the approach to adults in an anatomical approach. The upper lower airway and then the GI tract. In pediatric cough we think a lot about etiology, timeframe, and characteristics. As you mentioned, a moist versus dry cough. In pediatric cough, one of the approaches is to think about specific and nonspecific etiologies for cough. When I say specific, it refers to cough in the presence of symptoms that suggest an underlying etiology. And that's where in pediatrics, a very thorough history and exam is necessary when assessing children with cough. As in the majority of patients, specific cough etiologies can be defined in children. And unlike adults where cough characteristics have been shown to be of little diagnostic value, certain cough qualities such as a staccato cough are often very diagnostic in children. Recent studies have looked at larger groups of children and have found that etiologies of cough can be thought of as four specific categories and they include asthma, a protracted bacterial bronchitis, upper airway cough syndrome, and then a group of miscellaneous etiologies which include cardiac disease, foreign body pertussis and habit cough. I would make the point that in children gastro esophageal reflux is uncommon as an etiology of chronic cough. And of the four common specific conditions or etiologies of cough in children, cough variant asthma and protracted bacterial bronchitis are thought to be the most common.

Host: Yeah, I mean that's very interesting. Especially the point you know, made regarding mucus as a contributory factor to possible anatomic abnormalities because often and especially patients tend to associate any production of mucus with some type of infection or a specifically a bacterial infection. And often no, they feel antibiotics maybe the solution, but it is important, you know, to think out of the box ideas or diagnoses such as an anatomic issue. And I, you know, I couldn't agree more that it really does vary by children or adults and often there is a lot of confusion amongst even other clinicians who may be referring a patient or parents as well. So again, the managing of expectations and patient education is extremely important. On that note, I know Kevin you had mentioned you know, the prolonged bacterial bronchitis or protracted bacterial bronchitis as one of the most common etiologies in children. Could you expand more on that specifically its presentation and treatment.

Dr. Murphy: Yes. I'd be glad to mention a few things about protracted bacterial bronchitis as it's a very important condition that leads to chronic cough and presents as a chronic wet day and nighttime cough. And some children will have associated noisy breathing or wheezing. It's interesting that when one looks at bronchial alveolar lavage and these children, a couple of things are demonstrated that that really lead to the treatment of these children. The first is, is that close to 90% of these children who have protracted bacterial bronchitis will have increased numbers of neutrophils and will also have high colony counts of streptococcus pneumonia and Homophiles influenza. It's interesting too that as was mentioned, the anatomy plays a role as a number of these children will have underlying anatomical abnormalities such as tracheal Malaysia, Bronchio Malaysia or both. In fact, it's been reported that up to 75% of patients with protracted bacterial bronchitis, especially the younger children, will have underlying anatomical abnormalities. Important, especially based on bronchial Alveolar Lavage data is that treatment with high dose amoxicillin cationic acid can result in a significant resolution in almost all patients. However, it's been reported that as successful as the initial treatment, a number of patients will have recurrence of symptoms and will require repeated courses of antibiotics. Protracted bacterial bronchitis is an important consideration in thinking about children, especially younger children who have persisting chronic cough.

Dr. Sher: Kevin I'm an allergists. You're a pulmonologists. And I'm intrigued by the concept of PBB in that as an allergist we see a whole lot of chronic sinusitis with the same organisms that you're seeing in PBB. And what about the concept that actually PBB is the result of an undertreated or unrecognized chronic sinusitis that then seeds the lower lungs? With the treatment being the same, that if you treat with prolonged antibiotics for PBB, you may actually be treating the sinus infection along with the secondary bacterial bronchitis.

Dr. Murphy: It's interesting that you bring up the notion of in some ways how we used to think about the united or one airway. There is very good data in children that assessment of cough, particularly chronic cough with a simple waters view of the sinus can be helpful as findings of chronic sinus disease are common in children who present with cough and they respond very nicely to antibiotic therapy. I hadn't thought about it in the way that you presented things in regard to the upper airway leading to the lower airway. And now as I think about it, we see these younger children who have evidence of purulent nasal drainage, nasal congestion, and have this wet cough, if you will, that keeps them up at night and often is what brings them to our office. And it may well be, particularly if we can see these patients earlier in the disease, they may have a better response to antibiotic therapy before their lower airway is seated with pathogens particularly office influenza and strep pneumonia. So I really think it's important that you bring up this concept of thinking about the upper airway when discussing protracted bacterial bronchitis.

Host: So one question that came to my mind you know, being, we're all immunologists as much as allergists. Do you think that these children deserve an immune workup if they are having these protracted bacterial infections, whether it be in their sinuses or in their lungs?

Dr. Murphy: Well, I will start that discussion and look forward to Mandel's thoughts. I do think that chronicity always moves me into the direction of an initial immunological evaluation. And I say that in that as we get better at thinking about children with chronic cough and particularly thinking about specific etiologies that we can uncover in my experience it's less likely that they have underlying immune deficiency. However, if we're not able to define an etiology, certainly particularly those children with recurring upper airway infection and recurring infection and immunological evaluation would be important. Mandel, what's your thoughts and your experience in your pediatric population?

Dr. Sher: Well my other hat is a pediatric allergist immunologist down at Johns Hopkins. All children's, so have done this for about 35 years. So I appreciate the input. But you know, the rules are unusual infection, recurrent infections or prolonged infections. And I do suspect if someone is having PBB and it's taking a lot of antibiotics, and it's in a context of a history of having recurrent respiratory infections requiring antibiotics. I think an immunologic screen, looking for humoral immune deficiency is worthwhile.

Host: Great. Thank you. Shifting again away from the immune system. Mandel, what about the role of GERD or gastro esophageal reflux in cough? Are there any new thoughts there?

Dr. Sher: Absolutely Purvi. I appreciate that. And in contrast to what Kevin talked about regarding the minimal role of GERD in childhood it plays much more of a role in the adult with chronic cough. And this is an area that continues to really evolve regarding the role of acid or non acid reflux on the cause of chronic cough. We're really getting away from this concept of silent cough where cough is the only manifestation of upper, lower airway of GERD. And the recent recommendations based on data is showing that most of the GERD that's associated with cough does have some GERD symptoms be it heartburn, indigestion, regurgitation. And the recent recommendations are that you don't routinely give the multiple month course of PPIs just to rule out GERD. So this is the newer recommendations coming out. However, looking at the etiology of acid and non acid GERD is that there's always been this thought that you need the laryngeal Findra reflux.

The material needs to get up into the larynx to give you a redden throat or aspiration. And the role probably for most individuals where the gastrointestinal system is contributing to cough is probably through the vagal activation of the esophagus being distended or acid or non acid irritating the esophagus because that probably is a neurogenic signal coming from the gastrointestinal area that's activating this increase urge to cough, nociceptive hypersensitivity. So while we're getting away from quote empiric treatment of PPIs most of us who treat cough clearly do lifestyle measures to keep the lower esophageal sphincter closed. Coughing in itself will open up the LES, so coughing can be GERD. So we emphasize that no caffeine, limit the alcohol, limit the chocolate, limit that breath mints, limit the fatty foods, don't exercise after eating which is a real nice lifestyle approach to keeping that lower esophageal sphincter shot.

Dr. Murphy: Mandel, I was wondering your thoughts as you know, more and more allergists are doing rhino laryngoscopy in their office. Do you think there's a role, one for that procedure in an allergists office as part of the evaluation for chronic cough? Especially in adults and particularly when thinking about GERD?

Dr. Sher: Well, Kevin, I love that question because I do rhinoscopy, I've been doing it, I teach it, and as part as my cough lecture is, I find that next to phenol the most important diagnostic test in adults with chronic cough. Rhinoscopy not only will show upper airway disease, but it really looks at the anatomy and particularly function of the larynx. And most of the patients with cough hypersensitivity, which we will talk about, have a motor hyper function of their larynx and vocal cords. So you see paradoxical vocal foe movement, and also you see subtle hyper function of the vocal cords. And I see a significant number of unilateral vocal cord paresis in adults with chronic cough, which most likely was probably from a viral neuropathic injury, which then leads them to this cough hypersensitivity. So I'm a very strong proponent of nasal Laryngoscopy Faro gossipy. Looking at particularly not just again, anatomy, but function of the vocal cords.

Host: Thank you. That's a, that's an excellent point. I had one more question for Kevin. Actually. I know that the reflux or GERD is not as commonly manifesting as cough in the pediatric patients. What are some of the common manifestations of GERD in that population?

Dr. Murphy: I think you'd find that they are often similar to those of adults, although as we all know in younger children, it's often difficult to determine by the history if they're having the kind of symptoms, the burning the discomfort. One of the things that the children often say is that their tummy hurts or that they have a discomfort in their chest. And I think when that occurs, even though GERD is unusual in children it would make us think that that's a possibility and then an evaluation in that regard would be appropriate.

Host: Right. That's a great point. And something that we do see quite often in children this habit cough or habitual cough in pediatric patients. Kevin, can you expand a bit more on that and how you diagnose it?

Dr. Murphy: Yes, I'd be glad to. I think first of all in regard to rhino laryngoscopy, and habit cough that the College of Allergy has quite a role in this as they through the direction of Jack Sellner number of years ago initiated that the courses that still are very popular for allergists to learn and to understand the use of a rhino laryngoscopy. In the same way from a historical perspective, habit cough was initially described by Bernie Berman who was a past President of the American College of Allergy. And in his description is something that I think all of us see clinically is that those children who present with habit cough have a very loud, repetitive, dry barking cough. And what I think is most important in the history is this cough is absent once a child is asleep. One of the aspects of habit cough, it's very irritating to the family. And I think that for many of us who see these children, even for a brief period of time in the office have a sense of that irritation as it's very disturbing to others and interferes with school performance and often prevents children from attending school. The other aspect of habit cough is that it's often misdiagnosed as asthma and often I'll see patients referred that a child is having chronic cough and is not responding to asthma medicines, but indeed has habit cough. So in children with very disruptive day time cough without any other specific etiology, one should always think about and entertain the diagnosis of habit cough.

Host: Right. No, that makes, that makes complete sense. Mandel about cough hypersensitivity, going back to that can you speak to that? You know, us being allergists hypersensitivity is often something that we are asked to rule out, especially by our colleagues and even patients.

Dr. Sher: Well Purvi, cough hypersensitivity or cough hypersensitive syndrome is what we're left with as a diagnosis for those adults with chronic cough who you haven't found a cause or you've thought you found causes, but they're not responding to therapy. The typical patient is a 61 year old female who's been coughing multiple years. Cough is described as an increased tickle in their throat or 25% of them have that feeling in their upper chest. The men tend to be more throat clearers and the women will tend to have very difficulty problematic cough, again, leading to urinary and continents. The men sometimes will get syncope. Interesting enough. But it's uncommon but if I do see cough syncope, it will tend to be in a man. There's the feeling of postnasal drip as I mentioned, but little objective mucus, unless it's at the end of the cough. The cough does tend to be very dry, and the triggers tend to be talking, laughing smells, odors, change in temperature, air conditioning in Florida, when they turn on the car and the air conditioning goes on, they start coughing. Drinking cold liquids rather than eating all gives you the phenotypic history of cough hypersensitivity. These patients actually will not tend to cough during exercise and may actually make them feel better. Now, some of them may have associated anatomic contributions, but many of them also have that vocal cord involvement that Kevin asked about. They'll get hoarse, they can be raspy, they all talk to tightness in their upper chest and throat and vocal cord spasm can lead to shortness of breath. So this is kind of a phenotypic presentation that makes us not a diagnosis really of exclusion while we are excluding the component of other anatomic entities. But it gives you a history of multiple historical facts that you can check off that support the diagnosis of cough hypersensitivity.

Dr. Murphy: Mandel, I was wondering as I was listening to you talk about cough hypersensitivity in adults, in children, a habit cough does not occur once a child goes to sleep. What's the history in adults? Do they cough when they're sound asleep? If they have this cough, hypersensitivity?

Dr. Sher: Cough, a hypersensitive tends to extinguish during sleep, similar to habit cough and however the severe coughers I've seen will wake up at night, but waking up in the middle of the night out of a sound sleep to me is one of those warning signs. Similar to having copious mucus. One of the warning signs that encourage you to pursue an anatomic cause is having a cough actually wake you up. The historical point is you cough at night. It's not sufficient because what you'll find out is they've turned over, they'd got up to go to the bathroom, they're awake already. So the key, a historical point, is not, you just cough at night is do you, does the cough wake you up?

Dr. Murphy: That's interesting. It made me think about, the other question in talking to families is it's better to say once your child has fallen asleep do they stop coughing? Because often if you ask, does your child cough at night? They will say yes. Because they're thinking about as the sun goes down before the child goes to bed.

Host: Mandel, I had one quick question. Do you ever see itchiness as a feature of the hypersensitivity cough, either itchy throat or itchy ears?

Dr. Sher: That's a really interesting question because I look for these women. Do they have chronic pain? Do they have chronic itch? Most of them are primarily are just, the focus is on the, they pointed different areas, but usually that's super sternal notch, right? You know, and they point to it and I would say 75% of the patients do you go, what do you feel before you cough? And they point right to their lower throat. And but as an aside, in light of this triad of pain, itch and cough, you do see some of this autonomic dysfunction of irritable bowel, interstitial cystitis chronic headaches, in a certain subset. And the last point is it can be familial. So you see their grandmother had it, their mother had it, their daughter has it. So there is probably some genetic neurogenic disautonomic component which really needs further exploration by us.

Dr. Murphy: Mandel, one last question because I think cough hypersensitivity is so important. Do you find in your experience that this is more common in the overweight or obese patient?

Dr. Sher: So the data does support number one, it's Caucasian and that's true in the Western world versus other ethnic groups and there is a propensity to have a higher BMI in this, in these chronic cough populations.

Host: Thank you. That's very interesting. Thank you to our guests and to the listeners. That concludes part two of our three part series on cough from the American College of Allergy, Asthma and Immunology. Please be sure to join us for our final episode on treatment options. For other interesting episodes from Allergy Talk, please visit www.college.acaai.org/allergytalk. To receive CME credit for this or other eligible Allergy Talk podcasts. Visit education.acaai.org/allergytalk. I am Purvi Parikh for the American College of Allergy, Asthma, and Immunology.