Guideline
The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

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Abstract

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of “pathology-specific non-specific therapeutic drugs” and provide benefits to patients with chronic refractory cough.

Section snippets

Mechanism of cough development

Coughing is a physiological defense reaction that aims to eliminate the secretions retained in the airway or inhaled foreign substances outside the airway. Involuntary cough reflex with the vagal nerve as an afferent pathway and voluntary cough initiated via the cerebral cortex (e.g., urge to cough [1]) are involved in cough development (Fig. 1). An urge or feeling that one is likely to cough is the sensation that is generated before cough development when the cough receptor in the airway is

Definition of the terms related to sputum

Sputum is a general term for airway secretions expectorated from the lower airway (Table 3). After exceeding the physiological excretion capacity of mucociliary transportation, the secretions retained in the airway stimulate the cough receptors and are excreted as sputum by coughing (cough clearance). Excess airway secretions are mainly derived from mucin production in mucus-producing cells and hypersecretion. This reaction is not only triggered as a biological defense reaction against various

Management of acute cough (up to three weeks: see Flow Chart 1; Fig. 4)

The management of adult patients with acute cough (up to three weeks after onset) who present to hospital is shown in Flow Chart 1 (Fig. 4). The general procedure is shown below (3.1–3.4).

Management of prolonged or chronic cough (longer than three weeks: Flow Chart 2; Fig. 5)

When adult patients with a prolonged or chronic cough present to hospital (three weeks or more from the onset), there may be multiple etiologies, changes in etiology over time, or self-healing of post-infectious cough at play. Therefore, it is important to be flexible in your diagnosis, as described in ∗1 in Flow Chart 2 (Fig. 5). It is recommended first to explore whether there is a single or major cause of the cough. However, it should be noted that there may be multiple causes.

5-1 Recent topics and future perspectives

The basic tenet of this guideline is to first identify the causative disease(s) and then administer specific treatment without using non-specific therapeutic drugs as much as possible. However, a significant proportion of patients, especially those in specialty outpatient clinics, respond poorly to the treatment given for an assumed cause [14,56,57]. Recently, causative diseases such as organ-specific autoimmune diseases and ventricular premature contraction have been reported. In addition,

Conflict of Interest

Dr. Hiroshi Mukae received honoraria from Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., KYOLIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Taisho Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., and AstraZeneca K.K., a research grant from Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji

References (68)

  • P.J. Kahrilas et al.

    Chronic cough due to gastroesophageal reflux in adults: CHEST guideline and expert panel report

    Chest

    (2016)
  • A. Niimi

    Gastroesophageal reflux disease: an important consideration for respiratory disorders

    Respir Investig

    (2017)
  • B.J. Undem et al.

    Neural dysfunction following respiratory viral infection as a cause of chronic cough hypersensitivity

    Pulm Pharmacol Ther

    (2015)
  • Y. Kanemitsu et al.

    Clinical impact of gastroesophageal reflux disease in patients with subacute/chronic cough

    Allergol Int

    (2019)
  • K.F. Chung

    Chronic 'cough hypersensitivity syndrome': a more precise label for chronic cough

    Pulm Pharmacol Ther

    (2011)
  • A. Niimi et al.

    Evidence for neuropathic processes in chronic cough

    Pulm Pharmacol Ther

    (2015)
  • N.M. Ryan et al.

    Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial

    Lancet

    (2012)
  • A.E. Vertigan et al.

    Pregabalin and speech pathology combination therapy for refractory chronic cough: a randomized controlled trial

    Chest

    (2016)
  • A. Niimi et al.

    Interfering with airway nerves in cough associated with asthma

    Pulm Pharmacol Ther

    (2019)
  • R. Abdulqawi et al.

    P2X3 receptor antagonist (AF-219) in refractory chronic cough; a randomised, double-blind, placebo-controlled phase 2 study

    Lancet

    (2015)
  • S.B. Mazzone et al.

    Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging

    Am J Respir Crit Care Med

    (2007)
  • F. O'Connell et al.

    Capsaicin cough sensitivity decreases with successful treatment of chronic cough

    Am J Respir Crit Care Med

    (1994)
  • N. Ohkura et al.

    Bronchoconstriction-triggered cough in conscious Guinea pigs

    Exp Lung Res

    (2009)
  • I. Satia et al.

    Capsaicin-evoked cough responses in asthmatic patients: evidence for airway neuronal dysfunction

    J Allergy Clin Immunol

    (2017)
  • M. Takemura et al.

    Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma

    Respiration

    (2012)
  • K. Fukumitsu et al.

    Tiotropium attenuates refractory cough and capsaicin cough reflex sensitivity in patients with asthma

    J Allergy Clin Immunol Pract

    (2018)
  • M. Fujimura et al.

    Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid

    Thorax

    (1992)
  • Q. Liu et al.

    Characterization of increased cough sensitivity after antigen challenge in Guinea pigs

    Clin Exp Allergy

    (2001)
  • L.A. Becker et al.

    Beta2-agonists for acute cough or a clinical diagnosis of acute bronchitis

    Cochrane Database Syst Rev

    (2015)
  • N. Ohkura et al.

    Bronchoconstriction-triggered cough is impaired in typical asthmatics

    J Asthma

    (2010)
  • N. Ohkura et al.

    Heightened cough response to bronchoconstriction in cough variant asthma

    Respirology

    (2012)
  • D.C. Bolser

    Cough suppressant and pharmacologic protrusive therapy: ACCP evidence-based clinical practice guidelines

    Chest

    (2006)
  • J.A. Nadel

    New approaches to regulation of fluid secretion in airways

    Chest

    (1981)
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