Management of chronic refractory cough
BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5590 (Published 14 December 2015) Cite this as: BMJ 2015;351:h5590All rapid responses
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We read with interest Gibson and Vertigan’s excellent review on the management of chronic refractory cough(1).
In our experience there is also a cohort of patients who fulfil the definition of chronic refractory cough (i.e. no identifiable cause or the cough persists after investigation and treatment of cough related conditions) but these patients have a productive rather than dry cough.
The distinction between dry and productive cough has previously been reported to be unhelpful in identifying a cause for the cough (2). However, we find a significant number of cases of chronic productive refractory cough to be consistent with a distinct phenotype which we have termed adult protracted bacterial bronchitis (APBB) as it resembles the paediatric diagnosis of protracted bacterial bronchitis (3). Sputum cultures are often repeatedly positive for organisms including Haemophilus influenzae but may be negative despite repeat sampling. We have found a prolonged course of low dose azithromycin to be particularly effective in this condition and are currently evaluating this treatment further in a cohort of patients with these symptoms.
1. Gibson PG, Vertigan AE. Management of chronic refractory cough. BMJ (Clinical research ed). 2015;351.
2. Smyrnios NA, Irwin RS, Curley FJ. Chronic cough with a history of excessive sputum production : The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. CHEST Journal. 1995;108(4):991-7.
3. Martin MJ, Harrison TW. Causes of chronic productive cough: An approach to management. Respir Med. 2015;109(9):1105-13.
Competing interests: No competing interests
Sir,
Despite the wide-ranging and helpful nature of your article (2015;351:h5590), there was little mention of possible environmental factors in aggravating or mitigating refractory cough. I have been astonished over recent years by the number of householders who appear to be using de-humidifiers with seemingly no measure of need or effect. This, combined with the increasing use of central heating and electric fires, must surely exacerbate if not initiate the chronic dry coughs that are now so common. I have certainly "cured" or at least ameliorated several such amongst family and friends by drawing their attention to the need for mucosal moisture!
Yours sincerely,
John Elliott
Competing interests: No competing interests
Whipple's disease is a rare but potentially treatable cause of chronic cough(1).
This was exemplified by a 63 year old non-smoking man who presented with a 2 year history of chronic cough, and in whom chest radiography was initially negative. A subsequent computerised tomography (CT) scan of the chest showed mild interstitial pulmonary oedema and small bilateral pleural effusions and a small pericardial effusion. A CT scan of the abdomen showed extensive abdominal lymphadenopathy. Following exploratory laparotomy and excisional lymph node biopsy microbiologic testing revealed gram positive bacilli which were subsequently identified as Tropheryma whipplei. Within 2 months after initiation of a regimen consisting of intravenous ceftriaxone and trimethoprim-sulfamethoxazole the patient reported resolution of his cough(1).
Chronic cough was also a feature in a 40 year old man with Whipple's disease, and in whom endobronchial biopsy revealed nonspecific inflammation. The diagnosis of Whipple's disease was made when Tropheryma Whipplei was identified from a duodenal biopsy specimen. Following appropriate antibiotic treatment, chronic cough resolved within 15 days and did not recur on 4.6 year follow up.
References
(1)Damaraju D., Steiner T., Wade J., FitzGerald JM. A surprising cause of chronic cough. N Engl J Med 2015;373:561-6
(2)Urbanski G., Rivereau P., Artru L et al. Whipple Disease revealed by lung involvement A vase report and literature review. CHEST 2012;141:1595-1598
Competing interests: No competing interests
Among the potentially treatable causes of chronic cough(1), mention must also be made of giant cell arteritis(2). This was exemplified by a 57 year old man in whom cough was initially associated with influenza-like symptoms, namely, malaise, muscle aches,and fever. After receiving antibiotics for presumed pneumonia, muscle aches and malaise diminished but cough and fever persisted. He subsequently experienced 6kg weight loss and developed headache. Temporal artery biopsy was performed, and this showed typical histological stigmata of giant cell arteritis. All symptoms, including cough, responded promptly to prednisone 60 mg/day, and did not recur during maintenance therapy with prednisone 7.5 mg/day. He remained well on 1 year follow up. Although bronchoscopy was not performed, the authors of the report speculated that chronic cough was attributable to granulomatous involvement of the bronchial wall and inflammation of the peribronchial vasculature(2).
References
(1) Gibson PS., Vertigan AE. Management of chronic refractory cough. BMJ 2015;351:h5590
(2) Olopade CO., Sekosan M., Schraufnagel DE. Giant cell arteritis manifesting as chronic cough and fever of unknown origin. Mayo Clinic Proceedings 1997;72:1048-1050
Competing interests: No competing interests
Gibson and Vertigan have written, and the BMJ has published, an article (1) that claims to be both a state of the art review and a teaching module worth one CPD credit, which fails to acknowledge the importance of emotional factors in assessing and managing Chronic Refractory Cough (CRC).
The prevalence of depression amongst those with chronic cough is cited as though it is simply a result of cough. The cross-section paper (2) referred to found trait anxiety to be significantly higher in patients with chronic cough than the healthy general population and a third of the patient sample volunteered the observation that stressful situations precipitated their cough. And yet anxiety and depression are not identified in this review, either as possible causative factors or routes to treatment.
Despite noting that CRC has features in common with Chronic Pain Syndrome (which they appear to equate with Neuropathic Pain (see their table 1), the lessons from that area in terms of psychological management have not been picked up. The search term “psych” applied to this paper yields only “psychoeducation” which is limited to explaining to the patient that the treatment will be hard work, and helping them to set realistic goals. The authors appear to be trying to eliminate emotion altogether and re-defining it as “central neural mechanisms” supporting this with the unremarkable observation that functional MRI shows cortical activity during coughing.
The authors searched under a number of terms, but these did not include “psychogenic cough” or “habit cough”. This is no doubt linked to the publication last year of a twelve-author paper (3) in Chest recommending that these terms be abandoned due to difficulties in definition, but this is insufficient reason for leaving them out of their search, given that they were common terms up to the publication of the Chest paper, and will probably continue to be so afterwards. Neither did they search under “tic cough”.
If they had searched under these terms they would have found a wealth of literature. It is possible that, as practitioners apparently alien to the world of emotion, psychogenesis, family-systemic, cognitive-behaviour therapies, and unconscious process, they would have been put off by the lack of randomised-controlled trials, but this is not good enough. Before subjecting patients to expensive and intrusive tests, a general practitioner and, for that matter, a chest physician should be able to elicit and reflect on contextual and emotional factors for their possible role in causing cough, and therefore their potential to alleviating or cure it.
Instead they devote six paragraphs to the “recently introduced concept of cough hypersensitivity syndrome” despite its reliance on expert opinion and lack of agreement about mechanism. They do not appear to have consulted similarly expert psychiatric liaison or psychological medicine opinion at all. In this way, they are highly selective in the weight that they give to “useful concepts”.
I have previously written a similarly exasperated response (4) to a BMJ review and elearning module on constipation. It is simply not good enough to publish lengthy, supposedly comprehensive, review articles that appear to wilfully ignore the emotional, systemic, and psychological life or, for that matter, neurodevelopmental conditions as important as tic disorders. I do not particularly like the word “psychogenic” but I find it vastly preferable to the systematic elimination of psycho-emotional process from medicine. As an exam response this lengthy piece - that includes spurious detail such as the exact duration of cough required to obtain a diagnosis of “subacute cough” (3 – 8 weeks, apparently) but entirely ignores psychosocial factors - should result in a fail.
Refs.
(1) BMJ 2015;351:h5590.
(2) McGarvey L, Carton C, Gamble L, et al. Prevalence of psychomorbidity among patients with chronic cough. Cough 2006;2:4; doi:10.1186/1745-9974-2-4.
(3) Vertigan A, Murad M, Pringsheim T, et al. Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report. Chest 2015;148(1):24-31. doi: 10.1378/chest.15-0423.
(4) BMJ 2012;345:e7309.
Competing interests: No competing interests
Re: Management of chronic refractory cough
Dear Sir
I was disappointed but perhaps not surprised to read the review of management of chroninc cough by Gibson and Vetrigan1.
Sadly the authors have not addressed the high index of suspicion that physicians should have that chronic cough may be caused by GORD and the difficulty in assessing this on purely symptomatic grounds. Firstly cough may be the sole manifestation in up to 50% of patients with GORD 2. Furthermore with the introduction of pH Impedance testing it has become clear that many patients will experience both intestinal and non-intestinal symptoms secondary to non-acidic reflux. Consequently poor response to PPIs confers limited diagnostic certainty on clinical grounds3 that symptoms are nor reflux related while standard pH monitoring may incorrectly exclude reflux as the cause of cough in many patients. The magnitude of this patient cohort remains unclear but referral for impedance reflux testing should always be considered when an alternative diagnosis has been excluded.
Secondly the authors make no mention of the role of anti-reflux surgery in patients with GORD related cough. Both traditional laparoscopic fundoplication4 and more recently LINX reflux management system5 has been demonstrated to be very effective when indicated. Both techniques have been demonstrated to significantly reduce chronic cough symptoms in patients with GORD while KINX appears to confer significantly fewer of the side effects associated Nissen’s fundoplication which historically may have deterred referral for surgery6.
So many patients suffer debilitating GORD related symptoms which go unrecognised and untreated and we urge all clinicians dealing with these patients to consider the diagnosis and referral to a specialist centre for evaluation.
1. BMJ 2015;351:h5590
2. Irwin RS, Richter JE. Gastroesophageal reflux and chronic cough. Am J Gastroenterol. 2000 Aug; 95(8 Suppl):S9-14
3. Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: A multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006;55:1398–402.
4. Allen CJ1, Anvari M. Surg Endosc. Does laparoscopic fundoplication provide long-term control of gastroesophageal reflux related cough? 2004 Apr;18(4):633-7. Epub 2004 Mar 19.
5. Bonavina L1, Saino G, Bona D, Sironi A, Lazzari V. J Am Coll Surg. One hundred consecutive patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease: 6 years of clinical experience from a single center. 2013 Oct;217(4):577-85. doi: 10.1016/j.jamcollsurg.2013.04.039. Epub 2013 Jul 12.
6. Reynolds JL1, Zehetner J1, Wu P1, Shah S1, Bildzukewicz N1, Lipham JC2. Laparoscopic Magnetic Sphincter Augmentation vs Laparoscopic Nissen Fundoplication: A Matched-Pair Analysis of 100 Patients. J Am Coll Surg. 2015 Jul;221(1):123-8. doi: 10.1016/j.jamcollsurg.2015.02.025. Epub 2015 Mar 5.
Competing interests: No competing interests