Capsaicin cough sensitivity and the association with clinical parameters in bronchiectasis

Wei-jie Guan, Yong-hua Gao, Gang Xu, Zhi-ya Lin, Yan Tang, Hui-min Li, Zhi-min Lin, Jin-ping Zheng, Rong-chang Chen, Nan-shan Zhong, Wei-jie Guan, Yong-hua Gao, Gang Xu, Zhi-ya Lin, Yan Tang, Hui-min Li, Zhi-min Lin, Jin-ping Zheng, Rong-chang Chen, Nan-shan Zhong

Abstract

Background: Cough hypersensitivity has been common among respiratory diseases.

Objective: To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis.

Methods: We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5).

Results: Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35-7.83, P<0.01), HRCT total score between 7-12 (OR: 2.57, 95%CI: 1.07-6.173, P = 0.04), BSI between 5-8 (OR: 4.05, 95%CI: 1.48-11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48-12.93, P<0.01).

Conclusion: Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.

Conflict of interest statement

Competing Interests: Profs. Zhong and Chen declare that they have received Changjiang Scholars and Innovative Research Team in University ITR0961, The National Key Technology R&D Program of the 12th National Five-year Development Plan 2012BAI05B01 and National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer No. 2013BAI09B09. All other authors declared no potential conflict of interest. None of the funding sources had any role in the study. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Subject recruitment flowchart.
Figure 1. Subject recruitment flowchart.
We screened 180 subjects (157 bronchiectasis patients and 23 healthy subjects). Of these, 22 bronchiectasis patients and 1 healthy subjects dropped out, and finally the data of 135 bronchiectasis patients and 22 healthy subjects were analyzed.
Figure 2. Distribution of Log 10 C…
Figure 2. Distribution of Log10C2 and Log10C5 in bronchiectasis patients and healthy subjects.
The capsaicin cough sensitivity, calculated as the capsaicin concentration causing at least 2 (C2) and 5 (C5), was compared between bronchiectasis patients and healthy subjects. Bronchiectasis patients yielded markedly lower levels of C2 and C5, suggesting significantly higher capsaicin cough sensitivity than healthy subjects. The lines of the bar in each figure represented the 25% percentile, median and 75% percentile, respectively. Figure 2-A, distribution of Log10C2, Figure 2-B, Distribution of Log10C5. The asterisks in both Figures 2-A and 2-B denoted P<0.01.

References

    1. Baker AF (2002) Bronchiectasis. N Engl J Med 346: 1383–93.
    1. Tsang KW, Bilton D (2009) Clinical challenges in managing bronchiectasis. Respirology 14: 637–50.
    1. Ho JC, Chan KN, Hu WH, Lam WK, Zheng L, et al. (2001) The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. Am J Respir Crit Care Med 163: 983–8.
    1. Tsang KW, Zheng L, Tipoe G (2000) Ciliary assessment in bronchiectasis. Respirology 5: 91–8.
    1. Torrego A, Haque RA, Nguyen LT, Nguyen LT, Hew M, et al. (2006) Capsaicin cough sensitivity in bronchiectasis. Thorax 61: 706–9.
    1. Couto M, de Diego A, Perpini M, Delgado L, Moreira A (2013) Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions. J Investig Allergol Clin Immunol 23: 289–301.
    1. Hilton EC, Baverel PG, Woodcock A, Van Der Graaf PH, Smith JA (2013) Pharmacodynamic modeling of cough responses to capsaicin inhalation calls into question the utility of the C5 endpoint. J Allergy Clin Immunol 132: 847–55.
    1. Morice AH (2013) Chronic cough hypersensitivity syndrome. Cough 9: 14.
    1. Song WJ, Chang YS, Morice AH (2014) Changing the paradigm for cough: does ‘cough hypersensitivity’ aid our understanding? Asia Pac Allergy 4: 3–13.
    1. Klink ME, Dodge R, Quan SF (1994) The relation of sleep complaints to respiratory symptoms in a general population. Chest 105: 151–4.
    1. Chan KK, Ing AJ, Laks L, Cossa G, Rogers P, et al. (2010) Chronic cough in patients with sleep-disordered breathing. Eur Respir J 35: 368–372.
    1. Milross MA, Piper AJ, Norman M, Dobbin CJ, Grunstein RR, et al. (2002) Subjective sleep quality in cystic fibrosis. Sleep Med 3: 205–212.
    1. Olveira C, Olveira G, Gaspar I, Dorado A, Cruz J, et al. (2013) Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life. Qual Life Res 22: 597–605.
    1. Lee LY, Ni D, Hayes D Jr, Lin RL (2011) TRPV1 as a cough sensor and its temperature-sensitive properties. Pulm Pharmacol Ther 3: 280–5.
    1. Park HK, Oh SY, Kim TB, Bahn JW, Shin ES, et al. (2006) Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough. Thorax 12: 1070–5.
    1. Bessac BF, Jordit SE (2008) Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bathesda) 23: 360–70.
    1. Chung KF (2011) Chronic “cough hypersensitivity syndrome”: a more precise label for chronic cough. Pulm Pharmacol Thera 24: 267–71.
    1. Tsang KW, Chan KN, Ho PL, Zheng L, Ooi GC, et al. (2000) Sputum Elastase in Steady-state Bronchiectasis. . Chest 117: 420–6.
    1. Murray MP, Turnbull K, MacQuarrie S, Pentland JL, Hill AT (2009) Validation of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis. Eur Respir J 34: 125–31.
    1. Ma W, Yu L, Wang Y, Li X, Lu H, Qiu Z (2009) Changes in health-related quality of life and clinical implications in Chinese patients with chronic cough. Cough 25: 5–7.
    1. Laszio G (2005) ATS/ERS task force: Standardization of spirometry. Eur Respir J 26: 319–38.
    1. Zheng JP, Zhong NS (2002) Normative values of pulmonary function testing in Chinese adults. Chin Med J 115: 50–4.
    1. Tunney MM, Einarsson GG, Wei L, Drain M, Klem ER, et al. (2013) Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am J Respir Crit Care Med 187: 1118–26.
    1. Pasteur MC, Helliwell SM, Houghton SJ, Webb SC, Foweraker JE, et al. (2000) An Investigation into Causative Factors in Patients with Bronchiectasis. Am J Respir Crit Care Med 162: 1277–84.
    1. Anwar GA, McDonnell MJ, Worthy SA, Bourke SC, Afolabi G, et al. (2013) Phenotyping adults with non-cystic fibrosis bronchiectasis: A prospective observational cohort study. Respir Med 107: 1001–7.
    1. Pasteur MC, Bilton D, Hill AT (2010) on behalf of the British Thoracic Society Bronchiectasis (non-CF) Guideline Group (2010) British Thoracic Society guidelines for non-CF bronchiectasis. Thorax 65: i1–i58.
    1. Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, et al. (2014) The bronchiectasis severity index: An international derivation and validation study. Am J Respir Crit Care Med 189: 576–75.
    1. Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj A, et al. (2009) Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J 34: 843–9.
    1. Goeminne PC, Nawrot TS, Ruttens D, Seys S, Dupont LJ (2014) Mortality in non-cystic fibrosis bronchiectasis: a prospective cohort analysis. Respir Med 108: 287–96.
    1. Mandal P, Chalmers JD, Graham C, Harley C, Sidhu MK, et al. (2014) Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled study. Lancet Respir Med 2: 455–63.
    1. Varechova S, Plevkova J, Hanacek J, Tatar M (2008) Role of gender and pubertal stage on cough sensitivity in childhood and adolescence. J Physiol Pharmacol 59: 719–26.
    1. Goeminne PC, Vandooren J, Moelants EA, Decraene A, Rabaey E, et al. (2014) The sptuum color chart as a predictor of lung inflammation, proteolytics and damage in non-cystic fibrosis bronchiectasis: a case-control analysis. Respirology 19: 203–10.
    1. Chalmers JD, Hill AT (2013) Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol 55: 27–34.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever