Nocturnal Cough


Article Author:
Davinder Singh
Radia Jamil


Article Editor:
Kunal Mahajan


Editors In Chief:
Mark Pellegrini


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/9/2019 11:24:05 PM

Introduction

A cough is a symptom that has been experienced by every human being and is an essential protective and defensive act whose action secures the removal of mucus, noxious substances, and infections from the larynx, trachea and larger bronchi. Impairment or absence of the coughing mechanism can be dangerous and even fatal in disease. Women tend to a chronic cough more often and to have heightened cough reflex sensitivity compared to men. A nocturnal cough is distressing and disturbs one's sleep.[1]

Etiology

Causes of a nocturnal cough can be categorized as respiratory, non-respiratory and systemic. The most common respiratory causes of a chronic cough include post nasal drip, postinfectious, and asthma. Environmental factors include smoking, both active and passive; this is the most frequent environmental factor. Drugs include ACEIs, beta-blockers, and NSAIDs. Drugs causing pulmonary fibrosis are bleomycin, busulphan, methotrexate, carmustine, amiodarone, cyclophosphamide, and hydralazine. Other respiratory causes include bronchiectasis, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial lung disease (ILD), primary or secondary lung tumors, sarcoidosis, and tuberculosis. Other upper airway conditions to be ruled out are chronic tonsillar enlargement, obstructive sleep apnea, gastroesophageal reflux disease (GERD), laryngeal problems and foreign bodies in the large airways. Non-respiratory causes are GERD, recurrent aspiration, left ventricular failure, mitral stenosis, pulmonary infarction, and psychogenic a cough is a diagnosis of exclusion. Very rare conditions cardiac arrhythmias, aortic aneurysm, cough only when supine (due to a collapse of large airways), following complex involuntary tics (Tourette syndrome) and vitamin B12 deficiency (probably due to sensory neuropathy). Of all these conditions, cough variant asthma, GERD and upper airway cough syndrome (UACS) are called the pathogenic triad, and they constitute 90% cases.[2][3][4]

Epidemiology

A worldwide study from 16 countries has shown that a nocturnal cough was present in 30%, productive cough in 10%, and non-productive cough in 10%. Conditions such as chronic bronchitis are therefore grossly underrepresented, even though they cause considerable morbidity within the population. Similarly, such tertiary referral clinics are unlikely to represent the true prevalence of conditions such as asthma as a cause of a chronic cough, since at least in European practice, a therapeutic trial of anti-asthma medication is usually performed by the primary physician.[5][6]

Pathophysiology

Cough receptors are present in the pharynx and larynx, up to the segmental bronchi. Many types of sensory receptors respond to mechanical, inflammatory, thermal and chemical stimuli. These are connected to the vagal afferent nerves. The cough center located in the medulla and receives signals from these cough receptors. The efferent fibers reach the various muscles that produce the forced expiratory effort. Since the higher cortical centers influence the cough center, it is possible to produce or suppress a cough, voluntarily. The stimulation of a complex reflex arc is needed for each cough.[7]

History and Physical

A nocturnal cough needs to be assessed by intensity, severity, frequency, and sensitivity. Some clues in the assessment of a nocturnal cough:

  • A cough worsening on supine posture: Post nasal drip, esophageal reflux, chronic bronchitis, bronchiectasis, and heart failure
  • Presence of clear sputum: Hypersensitivity mechanism
  • Purulent sputum: Sinusitis, bronchiectasis; rule out tuberculosis
  • Blood tinged sputum: Malignancies, tuberculosis, and bronchiectasis
  • A non-productive cough: ACEI therapy
  • Improvement of a cough with antihistaminic treatment confirms the diagnosis of UACS
  • The red flag symptoms of chronic nocturnal cough are copious sputum (bronchiectasis), hemoptysis (malignancy, tuberculosis), systemic symptoms (tuberculosis, lymphoma, lung primary or secondaries) and significant dyspnoea (CCF, COPD, fibrotic lung disease).[8][3] Ask about a history of fever, weight loss, night sweats, and progressive fatigue.

General examination should evaluate clubbing (may be indicative of vasculitis, sarcoidosis, and malignancies), pedal edema and lymphadenopathy. Physical examination includes:

  • The search for a deviated nasal septum, turbinate hypertrophy, polyps, and sinusitis
  • Ears: Inflammation of the tympanic membrane or the external canal 
  • Respiratory system: Bilateral wheeze in COPD, bronchial asthma or even heart failure; Localized wheeze may occur in case of obstruction with a foreign body or tumor. 
  • Other systems should also be examined carefully

Evaluation

Chest X-ray is mandatory in all cases. A chronic cough with normal chest X-ray occurs with ACE inhibitor therapy, post nasal drip, GERD and asthma. These account for 90% of the cases. Diseases causing chronic cough but missed on chest X-ray include tumors, early ILD, bronchiectasis, and atypical mycobacterial pulmonary infection. Sputum examination is essential, wherever possible. Bacterial culture is needed if the sputum is purulent. Wherever feasible and in case of doubt, mycobacterial culture is also essential. A cytological examination is to identify malignant cells and to rule out eosinophilic bronchitis. Blood investigations to rule out infections, eosinophilia. ESR and CRP may give a clue to the presence of infection, malignancy and connective tissue disorders. Cold agglutinin titer for M.Pneumoniae, in suspected cases. HIV Elisa for AIDS. Possible further investigations include: B.Pertussis can be detected from the nasopharyngeal secretions. Induced sputum analysis, when sputum is not easily available and it is mandatory to examine the sputum. Bronchial provocation testing with methacholine or histamine is positive in bronchial asthma. Bronchoscopy is to be done after excluding all common causes if foreign body inhalation is suspected. Bronchoscopy is also indicated whenever there is abnormal chest X-ray, hemoptysis, obstructive lesions and infiltrates, that otherwise elude diagnosis. Echocardiography for cardiac ailments.  24hour ambulatory oesophageal PH or oesophageal manometry for diagnosing GERD. Radiology of the sinuses. HRCT – when no other diagnosis is made out.[2] Patients who have isolated chronic nocturnal cough, with a normal physical examination, chest Xray and spirogram are unlikely to have serious pulmonary conditions.

Treatment / Management

Encourage smokers to cease smoking.[9][10] A cough should improve within 8 weeks of smoking cessation. In the case of ACEI therapy, to stop the therapy. Improvement occurs within 4 weeks. Persistence of a cough after withdrawal of ACEIs raises the possibility of other causes of a cough. The onset of asthma has been linked to its use. Advising the patient to keep away from known environmental and occupational pollutants and irritants.

Treatment of UACS depends on a presumed etiology (infection, allergy or vasomotor rhinitis). So treatment includes first-generation antihistaminics, antibiotics, nasal saline irrigation, nasal pump sprays with glucocorticoids with or without decongestants like pseudoephedrine. Beta 2 agonists with inhaled corticosteroids give relief within a week’s time in case of proven asthma. A negative response to a bronchoprovocative test, eg. Methacholine rules out cough variant asthma. Peak Expiratory Flow Metre can be used as a cost-effective method to assess therapeutic response. A course of oral steroids for 2 weeks, or inhaled steroids,  gives relief in case of NAEB. A postinfectious cough can be treated with inhaled ipratropium, inhaled corticosteroids. Macrolide antibiotics with or without antitussives may be needed. GERD therapy includes prokinetic agents, H2 antagonists and proton pump inhibitors (PPIs). Appropriate dietary therapy and proper positioning of the patient in bed are important aspects of management. PPIs should be tried for 8 to 12 weeks.

Prognosis

Noctuurnal cough cause disturbed sleep, which initiate neuropsychiatric disorders in patients.

Deterrence and Patient Education

A nocturnal cough is a common and distressing symptom. It is important to identify and treat the cause for proper management.

Enhancing Healthcare Team Outcomes

Nocturnal cough is a common presentation with diverse etiology. The symptom is best managed by a multidisciplinary team including pulmonay nurses. In children, a trial or an anti-asthmatic medication may help make the diagnosis of asthma. But a thorough workup is required in adults because the cause may be a malignancy or a vascular pathology (Aneurysm).

The outcomes depend on the cause.


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Nocturnal Cough - Questions

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Which of the following is not in the differential diagnosis of nocturnal cough?



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Which of the following is not a common cause of nocturnal cough?



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Which is a false statement regarding an ACE-inhibitor-induced cough?



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Which of the following is not a component of cough reflex arc?



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Which of the following is not associated with a post viral infection cough?



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A 65-year-old female presents to her healthcare provider with the complaint of a cough for six weeks duration. She describes the cough as dry and pronounced, especially at night. This cough is accompanied by hoarseness and sore throat. On further questioning, she reports a sensation of burning in her chest and "indigestion" that is greater whenever she lies down. Her current medications include lisinopril, metformin, and atorvastatin, all of which she has been using for several months. She claims to have been a smoker for 15 years but quit recently. She denies any history of allergies, rhinorrhea, wheezing, or difficulty breathing. Which of the following is the most likely cause of her symptoms?

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Nocturnal Cough - References

References

Fell AKM,Svendsen MV,Kim JL,Abrahamsen R,Henneberger PK,Torén K,Blanc PD,Kongerud J, Exposure to second-hand tobacco smoke and respiratory symptoms in non-smoking adults: cross-sectional data from the general population of Telemark, Norway. BMC public health. 2018 Jul 6     [PubMed]
Guenter K,Cassel W,Hildebrandt O,Kroenig J,Fischer P,Weissflog A,Vogelmeier C,Koehler U, [Control of Respiratory Symptoms During Sleep in Patients with Stable Bronchial Asthma]. Deutsche medizinische Wochenschrift (1946). 2018 Sep     [PubMed]
Imai E,Hirai K,Mikami Y,Nukaga M,Enseki M,Tabata H,Kato M,Mochizuki H, An objective evaluation of nocturnal cough count and cough pattern in children with psychogenic cough. Respiratory investigation. 2017 Nov     [PubMed]
Hallit S,Leynaert B,Delmas MC,Rocchi S,De Blic J,Marguet C,Scherer E,Dufourg MN,Bois C,Reboux G,Millon L,Charles MA,Raherison C, Wheezing phenotypes and risk factors in early life: The ELFE cohort. PloS one. 2018     [PubMed]
Tang SP,Liu YL,Gao H,Dong L,Lin DR,Chen S,Zhang DY,Zhang LL,Pan J, [Correlation between severity of gastroesophageal reflux cough and degree of gastroesophageal reflux disease]. Zhonghua er ke za zhi = Chinese journal of pediatrics. 2018 Jul 2     [PubMed]
Cullinan P, Persistent cough and sputum: prevalence and clinical characteristics in south east England. Respiratory medicine. 1992 Mar     [PubMed]
Janson C,Chinn S,Jarvis D,Burney P, Determinants of cough in young adults participating in the European Community Respiratory Health Survey. The European respiratory journal. 2001 Oct     [PubMed]
Sharma S,Alhajjaj MS, Cough null. 2018 Jan     [PubMed]
Cabon E,Rey F,Tissier-Ducamp D,Del Volgo MJ,Delliaux S,Bues-Charbit M,Charpin D,Brégeon F, [Occurrence of delayed symptoms after a challenge test with methacholine]. Revue des maladies respiratoires. 2018 Mar     [PubMed]
Fazlollahi MR,Najmi M,Fallahnezhad M,Sabetkish N,Kazemnejad A,Bidad K,Shokouhi Shoormasti R,Mahloujirad M,Pourpak Z,Moin M, The prevalence of asthma in Iranian adults: The first national survey and the most recent updates. The clinical respiratory journal. 2018 May     [PubMed]

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