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- Cough -
5/31/05 re: Comparison of pertussis and asthma
I am looking for the comparison of pertussis, asthma, allergy, uri, vri, pneumonia, cough (both chronic and acute) in regard to signs, symptoms, and complications and treatment. If you can answer?
I wish to be of assistance to you but the broad-ranging questions you have asked would require responses in the equivalent of several textbook chapters. This is far in excess of what I can carry out in the relatively concise responses permitted in this Ask the Expert program. You also did not specify whether the questions you posed dealt with predominantly children or adults since the clinical pictures vary somewhat in the two age groups.
Therefore, I will pick one aspect of your questions - a comparison of pertussis infection (Pert) and asthma in adults. This question is of particular current importance because several studies have shown that Pert may be responsible for 20-30% of chronic cough in adults (see enclosed abstract of a very recent Perspectives article about this subject). However, many physicians think of Pert as a childhood infection and do not consider Pert as a cause of chronic coughing in adults. Recognition of Pert as a cause of chronic cough may also be decreased because Pert-induced cough in adults is often not accompanied by the "whoop" heard typically in childhood Pert infections.The situation is also complicated by the fact that chronic/recurrent cough may be the major (sometimes the only apparent) manifestation of persistent asthma. Indeed, asthma is one of the three most common causes of chronic cough with a negative chest X-Ray found in the extensive experience of Irwin and his group (post-nasal drip and G-E reflux being the other two-see enclosed abstract). Therefore, if an asthmatic has a chronic cough, it is often attributed to the hyper-reactive airways found in many asthmatics with worsening after certain viral respiratory infections.One should consider Pert as a possible diagnosis in chronic cough particularly if the patient had not received Pert immunization in childhood. Although physicians assume that all individuals received Pert immunization as part of the "baby shots" a number of parents refused the Pert component of such immunization about 30 years ago because of news reports about serious adverse effects of the whole cell Pert vaccine available at that time. Thus, there may be a sizable number of Pert-susceptible young-middle age adults.
I will attempt to answer more specific, focused questions about the other subjects you raised if you submit them separately in future Ask the Expert requests.
From Dworkin - Annals Intern Med- 2005;142:832-35Although studies have shown that pertussis is responsible for approximately 20% to 30% of cases of cough lasting more than 2 weeks in adults and adolescents, physicians have generally considered pertussis a disease that affects only children. Epidemiologic trends demonstrate that the incidence of pertussis has been rising, especially in adolescents and adults. Consequently, pertussis is not a "zebra" diagnosis but deserves a place among the community-acquired list of adult pathogens. Increased awareness among physicians about pertussis is important because adults may transmit the infection to infants, in whom the disease often leads to hospitalization and may result in death. Reporting this disease to the local health department is critical to its control because both case-patients and their close contacts should receive antimicrobial prophylaxis. A booster vaccine for adolescents and adults is likely to become available in the near future, so this is an important time to ensure that all physicians, not just pediatricians, are knowledgeable about the diagnosis, treatment, and reporting requirements for pertussis
Expert Opin Pharmacother. 2003 Jul;4(7):1039-48.
Pharmacotherapy of chronic cough in adults.
Madison JM, Irwin RS.
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA.Chronic cough is a debilitating symptom for which patients commonly seek medical attention. Among adult non-smokers who are not taking an angiotensin-converting enzyme inhibitor and have a normal or near normal chest radiograph, postnasal drip syndrome caused by a variety of rhinosinus conditions, asthma and non-asthmatic eosinophilic bronchitis and gastro-oesophageal reflux disease singly or in combination, are the most common diagnoses underlying chronic cough. Pharmacotherapy for chronic cough can be either specific or non-specific.
Specific therapy is preferable and the most effective as it is directed at the aetiologies and pathophysiological mechanisms responsible for cough. In contrast, non-specific therapy is used only in limited clinical settings, as it is directed at the symptom rather than underlying aetiologies and aims only to control, rather than eliminate cough.
5/30/05 re: Treatment of ACE inhibitor cough
Is picotamide being studied in the us for ace-inhibiter /dy cough? where? what do you know about this?
I have had no personal experience with the use of picotamide treatment for ACE inhibitor (ACEI)-induced cough. I could find only one report (by Malini et al) of a trial of picotamide in such cases (see abstract below). Therefore, I obtained expert input from Dr. Mark Dykewicz of the St. Louis Univ School of Medicine. Dr. Dykewicz has recently written a very good review of the cough and angioedema syndromes associated with ACEI therapy (see enclosed abstract). I have enclosed Dr. Dykewicz's prompt and thoughtful reply (just below). Unfortunately the attachment referred to in his response did not download adequately.
Dr. Dykewicz's commentsTo my knowledge, the Malini et al 1997 article is the only primary publication about the usefulness of picotamide for treating ACE inhibitor cough. After getting your email, I looked through my 2 inch stack of articles that I have about ACE-inhibitor induced angioedema and cough, and while I found a good number of articles that cite the Malini findings, I can find no other original research publications that have looked at the question. I suspect that because angiotensin 2 receptor blockade agents (ARBs) got released not long after the Malini article - and for most purposes ARBs have turned out to be reasonable substitute agents from ACE inhibitors - there was diminished need/impetus for looking at ways of treating ACE inhibitor induced cough.
As for my opinion about use of picotamide for ACE inhibitor cough, I think its use does make some mechanistic sense, and is compatible with the premise that inhibition of the kininase activity of ACE leads to increased bradykinin (and other kinin) levels that result in cough. To illustrate and summarize how this could all tie together, I have attached a Powerpoint slide that I pulled out of a drug allergy presentation that I published last year as part of the Current Views CME series. Using this as a framework for discussion, here is my understanding of some putative pathways that seem to make some sense, although I don't profess to thoroughly understand all the pathways, but at least this will give you a sense of what may be going on..1) The accumulation of kinins (cause by ACE inhibition) is speculated to initiate a cascade of events, first involving stimulation of vagal afferent nerves and non-myelinated c fibers, with consequent release of substance P.2) Although not indicated on my slide, this "build up" of substance P may also be potentiated more directly because kininase is thought to break down substance P itself , so kininase inhibition could also cause accumulation of substance P. However, I don't know if there are alternative pathways that can be used for break down of substance P which could reduce the importance of kininase inhibition in this respect.3) The next downstream step would be an interplay between substance P and arachidonic acid metabolites. For example, work that Peter Barnes has been involved with (see J Appl Physiol. 1992 Aug;73(2):649-53) has shown that PGE2 and PGF2 alpha can potentiate capsaicin induced cough. 4) In the Malini et al paper on the benefits of picotamide, they speculated that it isn't just the absolute levels of prostaglandins that may be important in causing cough, but that the relative levels of thromboxanes and prostaglandins may be important (an interplay which I crudely represented in the lowest "box" in the slide diagram).5) I ran across mention of another thromboxane synthetase inhibitor, ozagrel, that has been more recently studied for its antitussive effects, although not in the context of ACE inhibitor cough.Hope this helps. Best regards
Lancet. 1997 Jul 5;350(9070):15-8.
Thromboxane antagonism and cough induced by angiotensin-converting-enzyme inhibitor.
Malini PL, Strocchi E, Zanardi M, Milani M, Ambrosioni E.
Clinica Medica III, S Orsola University Hospital, Bologna, Italy.BACKGROUND: The increased prostaglandin synthesis that might follow stimulationof the arachidonic acid cascade by angiotensin-converting-enzyme inhibition(ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. METHODS: Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. FINDINGS: 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]).
INTERPRETATION: A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough
Curr Opin Allergy Clin Immunol. 2004 Aug;4(4):267-70.
Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management.
Dykewicz MS.
Division of Allergy and Immunology, Department of Internal Medicine,
Saint Louis University School of Medicine, St Louis, Missouri 63104, USAPURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. These drugs are commonly associated with cough, and are less commonly associated with angioedema, which may be potentially life threatening. This review describes data that extend our understanding of the mechanisms of these reactions, and provides guidance about clinical management. RECENT FINDINGS: For patients who develop angioedema from angiotensin-converting enzyme inhibitors, recent data are reassuring that the majority of such patients can tolerate angiotensin-II receptor blockers. These data support earlier conclusions that most patients with angiotensin-converting enzyme inhibitor-induced cough can tolerate angiotensin-II receptor blockers. Limited case reports suggest that in acute angioedema induced by angiotensin-converting enzyme inhibitors, patients refractory to standard treatment may benefit from the infusion of fresh frozen plasma. SUMMARY: Although data are incomplete, it appears that angiotensin-converting enzyme inhibitors cause cough and angioedema through a cascade of effects that begins with the accumulation of kinins, and then involves arachidonic acid metabolism and nitric oxide generation. Most patients who develop either cough or angioedema from angiotensin-converting enzyme inhibitors can tolerate angiotensin-II receptor blocking agents.
10/8/03 re: Cough of undetermined cause I did not find information on this troubling diagnosis. I have a patient with chronic cough resulting in paroxysms. Post nasal drip and rhinitis accompany cough. Triggers are irregular & inconsistent: laughing, eating, talking along with gustatory rhinitis, strong perfume, smoke etc. Frequently, no identifiable trigger. This is a life time non smoker. HRT, Fosamax, Calcium, multi vits are the only medications. She has been to see the following specialists: allergy x 3, ENT, internal med.
Gerd has been ruled out, spirometry testing negative, chest x-ray negative, treatment with inhaled cortisone did not result in stopping the cough, allergy skin testing negative. Multiple antihistamines have been tried...many too sedating for this 69 year old who weighs 118 lb. What next? Quality of life is being impaired.In the extensive experience of Irwin and his group, a prominent post-nasal drip (PND) is one of the most common "causes" of idiopathic cough with no evidence of chronic bromchial or pulmonary problems (see enclosed abstract). The presumed mechanism is that a particularly thick PND somewhat erratically hits sensitive areas in the hypopharynx with a resultant reflex-mediated cough. There is no evidence of which I am aware that the PND material actually goes down the bronchial tubes. Some of the people with this problem clear their throats frequently in an attempt to clear away the thick mucus lying there. Inhaled irritants including some strong odors may trigger the release if increased discharge within the nose which may add to the PND and aggravate the cough. One should consider the possibility of chronic sinusitis, particularly if the PND is purulent.
Another possible cause of recurrent cough with thick mucus in the posterior pharynx is a relatively recently described entity called pharyngoesophageal reflux. In this condition, there arrears to be an incompetence of the upper esophageal sphincter so that mucus is refluxed from the upper esophagus into the posterior pharynx causing episodic throat clearing and cough. To investigate this possibility one must have endoscopy performed by someone familiar with this type of problem.
I suggest a trial of systemic steroids starting with about 30 mg prednisone/day for 1 week and then tapering the dose to 0 over the next 10 days (assuming no absolute contra-indication to using this agent). Meanwhile get an expert ORL consultation, including sinus CT exam, with particular focus on the osteo-meatal complex area. If there is impressive improvement in the cough following the prednisone treatment, consider an immediate trial of nasal corticosteroid spray (e.g.- Flonase, Rhinocort) starting with 2 puffs bid then reducing to once daily to see if the improvement is maintained. One would not want to use systemic steroids chronically for this condition even if there is impressive improvement during the trial of therapy, particularly in an older woman with propensity to osteopenia. As noted in the enclosed abstract, Irwin believes that the older (and more likely sedating) H1 antihistamines are more effective for this PND than are the newer, non-sedating antihistamines. This is possible because the older agents frequently also have anti-cholinergic effects that may dry up some of the PND. However, I would prefer trials of nasal corticosteroid sprays as noted above.
_________________________________________________________Pulm Pharmacol Ther. 2002;15(3):261-6.
Diagnosis and treatment of chronic cough due to gastro-esophageal reflux disease and postnasal drip syndrome.
Irwin RS, Madison JM.
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Gastro-esophageal reflux disease (GERD) and postnasal drip syndrome (PNDS) are common causes of chronic cough. In patients with normal chest radiographs, GERD most likely causes cough by an esophageal-bronchial reflex. When GERD causes cough, there may be no gastrointestinal symptoms up to 75% of the time. While 24-h esophageal pH monitoring is the most sensitive and specific test in linking GERD and cough in a cause and effect relationship, it has its limitations. There is no general agreement on how to best interpret the test and it cannot detect non-acid reflux events. While some patients improve with minimal medical therapy, others require intensive regimens. Surgery may be efficacious when intensive medical therapy has failed. Because there are no pathognomonic findings of PNDS, the diagnosis is inferential and is based upon a combination of clinical findings, the results of ancillary testing, and the response to specific therapy. Specific therapy depends upon the rhinosinus disease(s) causing the PND. A common error in managing PNDSs is to assume that all H(1)-antagonists are equally efficacious. The second-generation, relatively non-sedating H(1)-antagonists have been found to be less effective than the first-generation agents in treating cough due to non-histamine-mediated PNDSs. Copyright 2002 Elsevier Science Ltd. All rights reserved.10/7/03 re: Recurrent coughing episodes in young children I'm a pediatrician. I have several patients, ages ranging from 2 to 6 yrs old, each with the same history of recurrent cough, each episode lasting 2-3 weeks. This occurs almost every month. These patients have already completed treatment for primary TB last year, but still have monthly cough and colds. On PE, all of them have no wheezing. Their cough is usually dry, some episodes are nocturnal, and some are not. Some respond to oral long-acting beta-agonists like bambuterol, some respond to Cetirizine, but they still occur almost on a monthly basis. Can I classify them as cough-variant asthma? If I give them a trial of oral prednisone and they improve, do I do this every time it recurs? Because my practice has been limited to adults for many years, I consulted Dr. Joel Fiedler of the Children's Hospital of Philadelphia for input in responding to your questions. Dr. Fiedler is a highly experienced Pediatric Allergist-Immunologist. His response is enclosed below. In many respects, it goes along with my thoughts based on experience in adults. Some points worth emphasizing: ________________________________________
- Check for the presence of wheezing an exercise challenge to detect possible underlying bronchial hyper-reactivity at a time when the patient does not have coughing episodes. It is generally not necessary to have formal exercise challenge equipment. Some of my colleagues have the children run around their office block for about 10-15 minutes (with a cooperative parent along side!), particularly if the weather is cold outside. If the child can carry out spirometry maneuvers, do such measurements before/after the exercise challenge. If no abnormalities noted after exercise, consider a cold air or methacholine challenge (need specialized facilities for this)
- The histories of your patients are quite unusual in that all were apparently treated for primary Tbc (based on just a positive PPD test?). I assume that the chest X-Rays in these children are now normal. I and Dr. Fiedler are unaware of Tbc casing recurrent cough if the Chest X-Ray is now normal and no evidence of miliary Tbc
- An impressive decrease in the cough with antihistamine therapy raises the possibility of chronic rhinosinusitis as a causal factor in the cough. As you are likely aware, one of the most common manifestation of chronic rhinosinusitis in young children is usually chronic cough, frequently worse at night.
- Gastro-esophageal reflux is generally considered as one of the more common causes of chronic idiopathic cough although the frequency of this relationship is still debated. Consider this if other causes not detected.
- Pertussis is assuming an increasing role as a cause of chronic cough in developed countries. This is generally seen in children who did not received the acellular pertussis vaccine, either because the parents refused it or the children received the older cellular pertussis vaccine (effective in only about 70% of vaccinees). However, I would not expect pertussis-caused cough to occur episodically.
- A single trial of systemic steroids given at the beginning of the coughing episode (assuming that no evidence of active Tbc) is reasonable to see if there is a response. However, Dr. Fiedler and I would not recommend using systemic steroids repeatedly at the frequent intervals you mention. If there is an impressive decrease in the cough during a trial of systemic steroids, try courses of inhaled steroids for recurrent episodes (the exact dose depending on the age of the child).
- I agree with Dr. Fiedler that the cause of the cough may not be the same in each child you referred to.
DR. FIEDLER'S RESPONSE:This is a tough one I am not sure whether tuberculosis will result in nonspecific hyperreactivity and for how long. It would seem unusual at the least to have that many patients with the same situation, all status post Tbc. Be that as it may the present situation does sound consistent with a trial of inhaled steroids rather than utilizing systemic steroids monthly in bursts, especially in patients with previous Tbc. I completely agree that before doing so I would do PFT's with assessing bronchodilator challenge (and if necessary a cold air challenge). In "typical" asthma that does not respond to expected treatment modalities, I also look for reflux and sinus disease, as you pointed out. Most of the children we see with chronic asthma do cough rather than wheeze, so that is not unusual, but there may be a mixed bag in the patients described as some do not have nocturnal cough and seem to respond to antihistamine which does raise possibility of postnasal drip with sinus disease. My own thought is that all these patients do not have the same problem. I hope this helps.3/12/02 re: Management of persistent cough in a 6-year-old child A six-year-old boy has been coughing since April of 2001. He has been on zyrtek, Claritin, albuterol, azmacort, singular and flovent as well as antibiotics. While taking erithimycin, albuterol and zyrtek the cough left but returned two months later. Azmacort seemed to quiet it some but it is still persistent and sometimes is a very loud cough. Please if you have any insights I would appreciate them. Because I have not treated young children for many years, I consulted Dr. Susan Schuval of the Long Island Jewish/North Shore Medical System, a highly experienced pediatric allergist who is a member of the Advisory Committee for our AADMC website. Her thoughtful response is enclosed below. "The differential diagnosis of chronic cough in a 6 year old is long but does include asthma, pneumonia (TB, pertussis, chlamydia, mycoplasma), sinusitis, gastroesophageal reflux, etc. Additional historical information that may be helpful includes further details on the nature of the cough (constant vs. intermittent, wet vs. dry, spasmodic, diurnal vs. nocturnal, seasonality. Has the child had any wheezing? Exercise intolerance? Fever? Weight loss? Sinus pain or tenderness? Are there any other family members who are coughing? What is his immunization status (has he received the full complement of DPT?-particularly pertussis-also what is his PPD status?)
You didn't mention your diagnostic evaluation but I would recommend a chest X-ray and spirometry (pre and post-bronchodilator) in any child who has been coughing for this long (11 months). If the cough is productive of sputum, I would send a Gram stain, routine bacterial cultures, and culture/smear for acid fast bacilli. Diagnosis of pertussis may require culture on special media (Bordet-Gengou agar). Sinus CT would be helpful in the diagnosis of sinusitis."
Susan Schuval, MD
"I would gear my treatment toward the results of the diagnostic evaluation rather than treating him with bronchodilators, inhaled steroids, antihistamines, and antibiotics. If spirometry reveals reversibility, I would continue treating the child for asthma. Diagnosis of infection would require a full course of antibiotics, depending on the pathogen."
2/6/02 re: Management problems in two infants What are your thoughts regarding following patients?
1. 1-yr. old child with no history of atopy on trying milk on 3 occ - 24-48 hrs after drinking 12 oz of milk develops hives. Pricks with fresh milk neg. She has been on Similac, eats yogurt, eggs with no problems.
2. 4 months old with life long history of chronic cough and runny nose. Otherwise healthy.I have not participated in the care of young children for many years. Therefore, I consulted Dr. Susan Schuval of the Long Island Jewish Hospital, a very experienced Pediatric Allergist and a member of the AADMC Advisory Committee. Her thoughtful response is enclosed below: "1. Immediate urticaria upon milk ingestion suggests IgE-mediated sensitivity to milk and I would have expected problems with other dairy products as well as a positive skin test to milk. It is possible that the rash is not truly urticarial but a coincident rash due to some cause other than milk allergy. Also possible is a non-IgE mediated sensitivity to milk, but again, I would expect the child to have problems with dairy products as well as milk. You could consider sending a RAST or CAP-RAST to further test for milk/milk protein {casein, lactoglobulin} to further assess the child's reaction. If these tests are negative, I would consider re-challenge with whole milk in 3-4 months.
2. The differential diagnosis of nasal congestion and cough in a 4 month old infant includes a long list of infectious diseases (congenital syphilis, tuberculosis, URI, sinusitis, infectious rhinitis, etc), anatomic abnormalities (choanal atresia, adenoidal hypertrophy), allergic diseases (asthma, rhinitis, food allergy), and genetic disease (cystic fibrosis). I would start with an inclusive physical examination directed at determining whether any pulmonary or nasal pathology is evident (check patency of nares, characterize nasal discharge-clear or greenish yellow-green, lung exam, growth parameters). Any chest abnormalities found on physical examination should be further evaluated by chest X-ray. Is there any family history of atopy, infection, cystic fibrosis, or other disease? If the cough and rhinorrhea are mild and the child is otherwise well, I would probably just treat empirically with diphenhydramine or hydroxyzine."
2/15/02 re: Evaluation of lingering cough An eight-year-old boy presents with a violent, hacking dry cough that has lingered for several weeks after an URI. He has experienced a similar pattern for the past two years. Chest x-ray is negative. Allergy testing done at age 6 was negative. He is no better one week after completing a course of Zithromax and taking Rhinocort nasal stray daily and Trimetic Cold and Cough (dextromethorphan HBr, Pseudoephedrine HCl and chlorpheniamine) tid. Interestingly, his mother has experienced the same pattern of coughing in years past. Her work-up for asthma was negative. She has obtained relief in the past from Zephrex XR and now from Rhinocort Aqua. Both mother and son find no relief in changing environments, as they annually travel from their home in Michigan to Florida for 7 - 10 days. I have read your recommendations for cough-variant asthma in adults and wonder if the same advice applies in pediatrics, or if you have any other suggestions.
The clinical picture you describe is not unusual in children as well as adults. In children with chronic cough and normal findings in a high quality chest x-ray, asthma, G-E reflux and post-nasal discharge are generally considered to be the three underlying disorders most commonly responsible. In a child, one might also want to rule out the presence of an aspirated foreign body (e.g., peanut). The situation in your patient is somewhat different. As I understand your description, the cough is not present all the time but occurs only for some weeks after a clear-cut respiratory infection. Therefore, it sounds as if bronchial hyper-reactivity (BHR) triggered by the respiratory infection is the most likely problem here. I do not know exactly what you mean by your comment that evaluation for asthma was negative. Individuals with post-infection BHR may often exhibit normal findings in standard pulmonary function tests but have evidence of BHR in a methacholine challenge tests. Sometimes, just the forced expiratory maneuver in pulmonary function testing may trigger severe coughing if the BHR is pronounced. Therefore, some physicians are reluctant to put a small child through such challenge procedures. Another approach I have used in adults (provided that the chest x-ray is normal and there is no evidence of an active bacterial infection) is a trial of moderate doses of prednisone (0.5 mg/kg wgt) for 10 days, tapering the dose over 2-3 weeks thereafter. If there is impressive improvement in the cough situation, add inhaled steroids to the treatment program as you begin to taper the oral prednisone dose and continue the inhaled steroids until the cough is minimal or gone. Although I do not personally take care of children, some of my pediatric allergist colleagues have told me that they have used a similar approach in a number of cases.
2/10/02 re: Use of cough suppressant in asthmatics I am a general pediatrician who trained in the era of preventive asthma care and take care of a number of asthmatics with strong emphasis on the use of preventive meds. stepping up and down with tx. I have recently seen several children treated by another practitioner for asthma exacerbations with albuterol nebs, PDN, as well as various preventives. In addition, these children were placed on cough suppressant meds. such as dextromethorphan or phenergan with codeine. I thought that the use of cough suppressants was contraindicated in asthmatics, particularly during an exacerbation of their symptoms, but I have not been able to find a reference to this topic in the Pediatric Asthma Guidelines nor in the Adult Guidelines.
I am presenting a program for parents of asthmatics with info on pathology, prevention, and therapy. (I recently presented it for another group and am refining the talk for a second presentation.) I would like to include something on the use or misuse of cough suppressants for asthmatics. Could you please send me one, or, if I am misinformed, please guide me?
Cough is a frequent manifestation of asthma. Sometimes, it is the only apparent manifestation of asthma so that asthma is considered by some as one of the 3 most common causes of a chronic, idiopathic cough with a normal chest x-ray (the others being G-E reflux and post-nasal discharge). However, I know of no accepted guidelines or recommendation of respected experts that includes the use of cough suppressants for the routine treatment of asthma. I could find no article recommending cough suppressant agents for asthma treatment in a Medline search. In most instances, appropriate anti-inflammatory treatment, particularly inhaled corticosteroids, will reduce, if not eliminate, such cough in asthmatic children, although this may take a little while to happen. Although usual doses of cough suppressants are often well tolerated, I can see some potential problems with their use in asthma, particularly in masking worsening asthma which is therefore not treated appropriately. Also, there may be G-I side-effects and adverse drug interactions (see abstract below). Indian J Pediatr 2001 Apr; 68 Suppl 2:S33-8
Pharmacological control of cough.
Maulik SK, Maulik M.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi."Cough constitutes an important medical problem in all ages. Although treatment of underlying pathologies, e.g., bronchial asthma, upper respiratory tract infection, etc. is well justified to cure cough, non-specific therapy in the form of a number of antitussive agents like, codeine, dextromethorphan, etc. is widely practiced to suppress it. Most of these agents are efficacious and well tolerated. Nevertheless, CNS toxicities may occur in newborns, especially those with immature metabolic profile. Some recent reports about interactions (involving hepatic cytochrome P450 enzymes) between dextromethorphan and other drugs are also noteworthy."
12/21/01 re: Cause of cough/asthma following surgery What would cause asthma-cough after open heart surgery? It is difficult to give a definitive response since you did not provide information about the exact nature of the open-heart surgery (OHS), whether the cough was dry or productive and what medications were being taken by the patient at the time of cough onset, etc. However, I have enclosed a few thoughts that might be considered. 1) Many patients undergoing OHS are given angiotensin converting enzyme inhibitor (ACEI) drugs prior to or at the time of surgery. In about 10% of such treated individuals, a dry cough is manifested starting at varying times after initiation of the ACEI therapy. In some cases, the patient may feel that they are wheezing although typical asthma is usually not present.
2) Beta-blocker drugs are also used commonly now as part of the treatment of congestive failure and some arrhythmias in patients undergoing OHS. Although the more recent beta blockers are more beta-1 specific, there may still be some degree of beta-2 blockade which can trigger cough and asthma in predisposed individuals.
3) If there has been pulmonary aspiration and decreased clearing of bronchial secretions possibly due to restricted chest movement because of post-op pain, atalectasis with associated cough may occur.
4) Occasionally, there is a disturbance of local neural pathways around the heart due to the trauma involved in certain OHS procedures. A reflex type of cough could result.
5/11/00 re: What is cough-variant asthma? What is cough variant asthma? What are the diagnostic criteria for it & how is it managed? I have described cough-variant asthma in the response to a previous Ask the Expert question (see next question) and in review of a good article about this subject to which I refer you for more details. However, not all lingering coughs associated with respiratory infections are asthma equivalents. Nor do they necessarily improve with inhaled steroids (see enclosed abstract). I believe a useful, practical therapeutic approach is:
- Check spirometry before and after inhaled albuterol. If >15-20% improvement in FEV1 after albuterol suggests as asthma.
- If diagnosis uncertain, consider doing inhalation methacholine challenge test.
- Trial of oral steroids (0.5 mg/kg/day) for 10-14 days If impressive decrease in cough occurs , taper oral steroids and add inhaled steroids at the same time.
Evaluating chronic cough
SUMMARY
Cough is reportedly the most common complaint for which people seek medical attention in the USA. Cough is a non-specific symptom associated with a variety of disorders. Post nasal drip, asthma, and G-E reflux (GERD) are the most commonly identified causes of chronic cough with other causes such as masses in or around the airways to be frequently considered. Poe and Israel of the University of Rochester have reviewed the recently promulgated guidelines of the American College of Chest Physicians (ACCP) for evaluation of cough. These include: 1) a thorough history and physical exam, including looking for clubbing and restriction of diaphragmatic movement; 2) chest x-ray; 3) first suspect post-nasal drip, asthma (including cough variant asthma where coughing is the predominant symptom) and GERD; 4) therapeutic trials for these conditions for adequate length of times, remembering that an individual patient may have more than one cause of cough; 5) note particular causes of cough in children and immunocompromised patients; 6) consider consultation if cough persists.REFERENCE - J Resp Dis 1999;20:343-47
EDITOR'S COMMENTS
I think that these guidelines are reasonable. The cough associated with post-nasal drip tends to be a tracheal type cough rather than the deep racking cough associated with lower airways problems. Although the ACCP recommends a therapeutic trial with a first generation antihistamine plus an oral decongestant for post-nasal drip, I have observed many patients in which this did not lead to impressive improvement. Nasal steroid therapy may be more effective but it may take weeks before impressive improvement is seen. In really puzzling cases of cough, a trial of corticosteroids (at least 0.5 mg/kg/day) for at least 10 days will usually suppress the cough associated with post-nasal drip and asthma. If the cough is unabated, other causes should be sought. If patient compliance with medication use during such a therapeutic trial is questionable, one can give a single injection of adequate dose of depo-steroids after the initial evaluation and then observe for 2 weeks to see if cough is reduced impressively
Effect of budesonide on chronic cough
Summary
Several studies have concluded that chronic idiopathic cough in some adults may be manifestation of chronic unrecognized asthma even though wheezing and dyspnea were not present. (See reviews in this Current Lit Section). One would expect clinical improvement in such 3cough-equivalent2 asthma cases following use of inhaled steroids. Pizzichini et al of the University of Santa Catarina in Brazil have reported a double-blind trial of inhaled budesonide (Bud) 400 microg. bid in 44 adults with chronic cough (> one year duration), 32 of whom were non-smokers. Induced sputum at baseline contained a modestly elevated proportion of neutrophils in 59% of subjects, associated with increased levels of IL-8. There were also increased levels of plasma proteins. Although sputum levels of eosinophil cationic proteins correlated with IL-8 levels, no increase in sputum eosinophils were seen in any subject. There was no significant reduction of cough by the Bud treatment.Reference
Can Resp J 1999;6:323-30Editor's Comments
These findings are part of a long-standing debate about the value of inhaled steroids in chronic cough. It has been shown that smoking-related chronic bronchitis is generally helped more by inhaled steroids when sputum eosinophilia is present. In my experience, impressive improvement following inhaled steroid use in idiopathic chronic cough is generally seen only in those with sputum eosinophilia, decreased FEV-1 (even though no wheezing), or bronchial hyperreactivity to methacholine3/22/00 re: Ineffectual treatment for chronic cough I am a pharmacist and I have a patient who presents with a persistent annoying cough. He has been diagnosed with "cough variant asthma" and is currently taking Flovent- 2 puffs BID, Serevent 2 puffs BID and Singulair-1T HS. He is still coughing terribly and I was just wondering, is this really the best therapy? You are correct that a chronic dry cough without typical asthmatic symptoms (wheezing, dyspnea) is sometimes considered to be an atypical presentation of asthma and treated thus. Indeed such "hidden asthma" is considered by some authorities to be one of the 3 most common causes of a chronic dry cough with a negative chest x-ray (the others being post-nasal discharge and gastro-esophageal reflux disease). (See below my review of such articles in the Current Literature Section of this website). Yet, recent studies have found that anti-asthma treatment may help only a minority of such cases (see enclosed review by me of a recent report). As stated there, I have found that individuals with true "cough-equivalent asthma" often have decreased airflow in pulmonary function testing, even when the patient is not obviously wheezing. At the very least, they have evidence of bronchial hyper-reactivity in methacholine challenge testing. If one induces sputum by inhalation of hypertonic saline aerosol, there are increased eosinophils.
I have found that a trial of prednisone (30mg/day for the average size adult) for 10 days is a good pragmatic probe. If there is no impressive decrease in cough, they usually don't have asthma. If the cough decreases, then a trial of inhaled steroids is indicated. The oral steroid dosage must then be gradually tapered.
2/3/00
Effect of budesonide on chronic cough
Summary
Several studies have concluded that chronic idiopathic cough in some adults may be manifestation of chronic unrecognized asthma even though wheezing and dyspnea were not present. (See reviews in this Current Lit Section). One would expect clinical improvement in such 3cough-equivalent2 asthma cases following use of inhaled steroids. Pizzichini et al of the University of Santa Catarina in Brazil have reported a double-blind trial of inhaled budesonide (Bud) 400 microg. bid in 44 adults with chronic cough (> one year duration), 32 of whom were non-smokers. Induced sputum at baseline contained a modestly elevated proportion of neutrophils in 59% of subjects, associated with increased levels of IL-8. There were also increased levels of plasma proteins. Although sputum levels of eosinophil cationic proteins correlated with IL-8 levels, no increase in sputum eosinophils were seen in any subject. There was no significant reduction of cough by the Bud treatment.Reference
Can Resp J 1999;6:323-30Editor's Comments
These findings are part of a long-standing debate about the value of inhaled steroids in chronic cough. It has been shown that smoking-related chronic bronchitis is generally helped more by inhaled steroids when sputum eosinophilia is present. In my experience, impressive improvement following inhaled steroid use in idiopathic chronic cough is generally seen only in those with sputum eosinophilia, decreased FEV-1 (even though no wheezing), or bronchial hyperreactivity to methacholine.6/1/98 re: cough syncope I am completely stymied about a patient with post-tussive syncope that is unrelenting for almost 6 weeks! Worked up extensively by cardiology, pulmonology, neurology and internal medicine without resolution of the problem. Has been arbitrarily treated with cortisone (past history of asthma), Tegretol (with the thought that it might be epileptic), codeine (to suppress the cough) and had a pacemaker inserted for bradyarythmia (with the hope that that was the problem). None of that resulted in any improvement! He has now been having a progressive increase in his sedimentation rate (to over 100) an his LDH (to 700+), his WBC count has also been rising to 14,000 (no fever or any evidence of active infection). Work up for lymphoma has also been negative so far. All other work up has been essentially negative. Do you have any suggestions and can you offer any help? As you likely know, cough syncope is a difficult clinical problem with often obscure etiology. Most individuals are smokers or ex-smokers. It sounds as if your patient has been investigated extensively. Some suggestions:
- Rule out G-E reflux, - commonly associated with cough syncope.
- Have patient wear a long-term cardiac monitor to pick up possible transient arrhythmia just before syncope episode.
- The very high sed rate in a patient may suggest lympho-proliferative process, myeloma, chronic infection such as SBE, or giant cell arteritis. Lymphoma masses in certain critical areas, of the mediastinum, even of small size could possibly trigger a cough/syncope. Detection of such a mass may require fairly sophisticated imaging studies.
