Life-Threatening and Non-Life-Threatening Complications Associated With Coughing: A Scoping Review

Richard S Irwin; Natasha Dudiki; Cynthia L French; CHEST Expert Cough Panel

doi:10.1016/j.chest.2020.06.012

. 2020 Jun 19;158(5):2058–2073. doi: 10.1016/j.chest.2020.06.012

Life-Threatening and Non-Life-Threatening Complications Associated With Coughing

A Scoping Review

Richard S Irwin ^1,^∗, Natasha Dudiki ¹, Cynthia L French ¹; CHEST Expert Cough Panel^1,^∗, on behalf of the

PMCID: PMC8640838 PMID: 32565267

Abstract

Background

This is an update of the section on complications that are associated with coughing in the 2006 CHEST cough guidelines that addresses two aims: (1) to systematically identify and thematically categorize the diverse complications of cough by providing a guide for future studies and (2) to identify gaps in the literature for future research.

Research Question

What are the potential complications that are associated with the act of coughing that have been reported in infants, children, adolescents, and adults?

Study Design and Methods

A scoping review was performed with the use of PubMed and SCOPUS databases that were searched from their beginning until September 6, 2019.

Results

Two hundred forty-seven publications met our inclusion criteria. To these, we added 38 articles from the 2006 complications paper that were not identified in the literature search plus the paper itself for a final total of 286 publications that formed the basis of this review. Since 2006, three new categories of complications have been reported: ear, nose and throat; disease transmission; and laboratory testing. Multiple additional complications that fall outside of these three categories have also been identified and included in the following categories: cardiovascular, constitutional symptoms, dermatologic, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial/quality of life, and respiratory. Not previously highlighted is that some of the complications led to serious morbidity that included death, especially in patients with comorbid conditions, and potentially resulted in harm to others when cough resulted in a motor vehicle accident.

Interpretation

Our work identified a large number of cough complications that we thematically categorized primarily by organ system so that future studies of each system or each complication can be conducted. The gap in the literature that future studies should address is to identify the frequency of the complications and the strength of their association with cough. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications. In the meantime, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications that are associated with coughing.

Key Words: complication, cough, organ system

Abbreviations: CQLQ, cough quality of life questionnaire

FOR EDITORIAL COMMENT, SEE PAGE 1818

This review provides an update to our article on the topic of complications associated with coughing in the 2006 American College of Chest Physicians Clinical Practice Guidelines on the Diagnosis and Management of Cough.¹^,²

As previously stated in 2006,¹ complications that are associated with coughing stem from physiologic events that teleologically seem to be designed to allow cough to carry out its two main protective functions: to prevent foreign material from entering the lower respiratory tract and to clear foreign material and excessive secretions from the lower respiratory tract. During the physiologic phases of coughing (ie, inspiratory, compressive, and expiratory), sufficiently high expiratory velocities are generated to carry out the aforementioned functions. The potentially injurious nature of these physical forces is recognized; for example, during vigorous coughing, intrathoracic pressures can reach 300 mm Hg³ that help to generate expiratory velocities up to 500 miles per hour⁴ (ie, 85% of the speed of sound).

From a cardiovascular standpoint, the physiologic effects of coughing can be a two-edged sword. Because intrathoracic pressures generated during coughing may hemodynamically compare favorably with chest compressions, cough CPR can be successfully used in a controlled environment.⁵ Because vigorous coughing can also generate intrathoracic energies up to 25 J,⁶ cardiologists, in a monitored in-hospital cardiac catheterization laboratory, often instruct patients, before the procedure begins, to vigorously cough when instructed to do so, if and when awake patients experience ventricular tachycardia and asystole during cardiac catheterization procedures. Because coughing can also be associated with a reflex increase in vagal tone, coughing can interrupt aberrant conduction of atrioventricular junctional tachycardia.⁷ On the other hand, coughing can also lead to atrioventricular block⁸ and other arrhythmias (Table 1).

Table 1.

Cough-Associated Complications

System Category	Complication
Cardiovascular	*Aortic dissection*¹⁴
	Arterial hypotension³^,¹⁵^,¹⁶^,¹⁷^,¹⁸^,¹⁹
	Arrhythmia
	• Bradyarrhythmias with or without heartblock with and without dizziness and syncope⁸^,²⁰^,²¹^,²²^,²³^,²⁴^,²⁵^,²⁶^,²⁷
	• Tachyarrhythmias, atrial, or ventricular²⁸^,²⁹^,³⁰
	*Coronary artery dissection*³¹^,³²
	*Cardiac luxation after pneumonectomy*³³
	*Stress cardiomyopathy*³⁴
	Dislodgement/malfunctioning of intravascular catheters*or other intravascular devices*³⁵^,³⁶^,³⁷^,³⁸^,³⁹^,⁴⁰
	Loss of consciousness³^,¹⁵
	*Pneumopericardium during coronary angiography*⁴¹
Constitutional symptoms	Excessive sweating, anorexia, exhaustion, temperature elevation (various combinations), vomiting⁴²
Dermatologic	Petechiae and purpura⁴³
	Disruption of surgical wounds (sternal and abdominal)⁴⁴^,⁴⁵^,⁴⁶
	*Subcutaneous hematoma not anticoagulated*⁴⁷^,⁴⁸^,⁴⁹^,⁵⁰
	*Subcutaneous hematoma receiving anticoagulation therapy*⁵¹^,⁵²
Ear, nose, and throat	*Arytenoid subluxation with or without obliteration of cricoarytenoid space*⁵³^,⁵⁴
	*Hemotympanum*⁵⁵
	*Thyroid cartilage fracture with phlegmon*⁵⁶
GI	*Esophageal rupture*⁵⁷
	*Gastroduodenal artery pseudoaneurysm rupture*⁵⁸
	Gastroesophageal reflux events⁵⁹
	Gastric hemorrhage after percutaneous endoscopic gastrostomy⁶⁰
	Gastric perforation after upper endoscopy⁶¹
	Hepatic cyst rupture⁶²
	*Laceration of stomach and spleen*⁶³
	Malfunction of gastrostomy button⁶⁴
	Mallory-Weiss tear⁶⁵^,⁶⁶
	Rectal prolapse with rupture of distal colon and evisceration of small intestine through anus and death in an infant⁶⁷
	Small bowel herniation through laparoscopic trocar site⁶⁸
	Splenic rupture⁶⁹^,⁷⁰^,⁷¹^,⁷²^,⁷³
	*Spontaneous retroperitoneal bleed with hematoma*⁷⁴
	*Inguinal or femoral or umbilical or lumbar or abdominal wall hernia*⁷⁵^,⁷⁶^,⁷⁷^,⁷⁸^,⁷⁹^,⁸⁰^,⁸¹
Genitourinary	Inversion of bladder through urethra⁸²
	Urinary incontinence⁷⁷^,⁸³^,⁸⁴^,⁸⁵^,⁸⁶^,⁸⁷
	*Vaginal cuff dehiscence with evisceration of ileal loops*⁸⁸
Musculoskeletal	*Avulsion of lesser trochanter of femur*⁸⁹
	From asymptomatic elevations of serum creatinine phosphokinase to rupture of rectus abdominus muscles with and without hematoma⁵¹^,⁹⁰^,⁹¹^,⁹²^,⁹³^,⁹⁴^,⁹⁵^,⁹⁶^,⁹⁷^,⁹⁸^,⁹⁹^,¹⁰⁰^,¹⁰¹^,¹⁰²^,¹⁰³
	*Diaphragmatic rupture with abdominal content herniation (small bowel and omentum)*¹⁰⁴^,¹⁰⁵^,¹⁰⁶
	*False-positive PET scan uptake in muscle related to cough*¹⁰⁷
	*Intercostal muscle rupture with lung herniation*¹⁰⁸^,¹⁰⁹^,¹¹⁰
	*Lung herniation through rib separations*⁴⁹^,¹¹¹
	*Lung herniation through previous incision*¹¹²
	*Liver, colon, small bowel, omentum, and lung herniation through transdiaphragmatic intercostal separation*¹¹³
	*Intercostal artery rupture and hematoma with or without hemothorax with or without rib fracture*⁴⁷^,¹¹⁴^,¹¹⁵^,¹¹⁶
	*Internal oblique muscle tear with hematoma*¹¹⁷^,¹¹⁸
	*Osteophytes of the ribs*¹¹⁹
	Rib fractures⁴⁷^,⁷⁸^,¹²⁰^,¹²¹^,¹²²^,¹²³^,¹²⁴^,¹²⁵^,¹²⁶^,¹²⁷^,¹²⁸^,¹²⁹^,¹³⁰^,¹³¹^,¹³²^,¹³³^,¹³⁴^,¹³⁵^,¹³⁶^,¹³⁷^,¹³⁸^,¹³⁹^,¹⁴⁰
	*• Costal margin separation with or without rib fracture and diaphragmatic rupture with abdominal visceral herniation into thoracic cavity or abdomen and/or subcutaneously*¹⁴¹^,¹⁴²^,¹⁴³^,¹⁴⁴^,¹⁴⁵^,¹⁴⁶^,¹⁴⁷^,¹⁴⁸
	*• Rib fracture with pseudohernia of abdominal contents*¹⁴⁹
	*• Rib fracture with lung herniation with or without pleural effusion*¹⁵⁰^,¹⁵¹^,¹⁵²^,¹⁵³^,¹⁵⁴
	*Scapula fracture*¹⁵⁵
Neurologic	Acute cervical radiculopathy and disc herniation¹⁵⁶
	*Carotid artery dissection and pseudoaneurysm¹⁵⁷***
	*Carotid artery dissection with stroke¹⁵⁸***
	*Cerebral air embolism causing stroke with and without death*¹⁵⁹^,¹⁶⁰^,¹⁶¹^,¹⁶²
	Cerebral spinal fluid rhinorrhea¹⁶³^,¹⁶⁴
	*Cervicobrachial pain¹⁶⁵***
	Cervical epidural hematoma associated with oral anticoagulation¹⁶⁶
	Cough syncope¹⁷^,¹⁶⁷^,¹⁶⁸^,¹⁶⁹^,¹⁷⁰^,¹⁷¹^,¹⁷²^,¹⁷³^,¹⁷⁴^,¹⁷⁵^,¹⁷⁶^,¹⁷⁷^,¹⁷⁸^,¹⁷⁹^,¹⁸⁰^,¹⁸¹^,¹⁸²^,¹⁸³^,¹⁸⁴^,¹⁸⁵^,¹⁸⁶^,¹⁸⁷^,¹⁸⁸^,¹⁸⁹^,¹⁹⁰^,¹⁹¹^,¹⁹²^,¹⁹³^,¹⁹⁴^,¹⁹⁵^,¹⁹⁶^,¹⁹⁷^,¹⁹⁸^,¹⁹⁹^,²⁰⁰^,²⁰¹^,²⁰²^,²⁰³^,²⁰⁴^,²⁰⁵^,²⁰⁶
	*Cough syncope causing car crash with injuries*¹⁸⁷
	*Cough syncope causing traffic accident*¹⁹¹
	*Cough syncope causing traffic accident with death of pedestrians*¹⁹⁰
	*Cough-induced anoxic cerebral injury in child*²⁰⁷
	*Cough-induced cluster headache*²⁰⁸
	*Cough-induced transient ischemic attack*²⁰⁹
	*Cough-induced nystagmus*²¹⁰
	*Cough-induced recurrence of spinal anesthesia*²¹¹
	*Cough-induced vertigo*¹⁹²
	Cough headache⁷⁷^,²¹²^,²¹³^,²¹⁴^,²¹⁵^,²¹⁶^,²¹⁷^,²¹⁸^,²¹⁹^,²²⁰^,²²¹^,²²²^,²²³^,²²⁴^,²²⁵
	*Cough headache presenting as toothache*²²⁶
	*Cough-induced hemiparesis*²²⁷
	*Cough-induced hemiplegic migraine*²²⁸
	*Cough-induced myxoma embolism causing paraplegia*²²⁹
	Dizziness²³⁰
	Cough-induced seizures¹⁷²^,¹⁷⁶^,¹⁸⁵^,²⁰¹^,²³¹
	Malfunctioning ventriculoartrial shunts²³²
	*Pneumocephalus*²³³
	*Pneumorrhachis*²³³^,²³⁴^,²³⁵^,²³⁶
	*Spontaneous dissection of cerebral arteries*²³⁷
	Stroke due to vertebral artery dissection²³⁸^,²³⁹^,²⁴⁰
	*Stroke due to bilateral carotid artery thrombus formation*²⁴¹
Ophthalmologic	*Extrusion of ocular contents during surgery*²⁴²
	Spontaneous compressive orbital emphysema of rhinogenic origin²⁴³
	*Orbital emphysema compressing the eyeball and the optic nerve*²⁴³
	*Periorbital ecchymosis (Panda sign)*²⁴⁴^,²⁴⁵
	*Subconjunctival hemorrhages*⁷⁷^,¹⁸⁰^,²⁴⁵^,²⁴⁶
	*Retinal detachment*²⁴⁷
	*Subhyaloid hemorrhage*²⁴⁸
	*Suprachoroidal hemorrhage*²⁴⁹^,²⁵⁰
	*Transient blindness*²⁵¹
	*Postoperative Trabeculectomy bleb leak*²⁵²
Psychosocial/quality of life	Fear of serious disease²³⁰^,²⁵³^,²⁵⁴
	Lifestyle changes²³⁰^,²⁵⁴^,²⁵⁵
	Self-consciousness²³⁰^,²⁵⁴^,²⁵⁵
	*Adverse effects on quality of life*⁸⁷^,²⁵⁴^,²⁵⁵^,²⁵⁶^,²⁵⁷^,²⁵⁸^,²⁵⁹^,²⁶⁰^,²⁶¹^,²⁶²^,²⁶³^,²⁶⁴
Respiratory	*Apical lung herniation with tracheal displacement*²⁶⁵
	*Chylothorax*²⁶⁶
	Diaphragmatic rupture with herniation of small intestine or stomach into chest⁶³^,²⁶⁷
	Exacerbation of asthma²⁶⁸
	*Hemothorax*¹¹⁶^,¹⁴⁴
	Herniations of the lung (eg, intercostal and supraclavicular) with and without incarceration²⁶⁹^,²⁷⁰^,²⁷¹^,²⁷²^,²⁷³
	Hydrothorax in peritoneal dialysis²⁷⁴
	*Hydropneumothorax and tension pneumothorax*⁵⁷
	Laryngeal trauma (eg, laryngeal edema and hoarseness)²³⁰^,²⁵⁴^,²⁵⁵^,²⁷⁵^,²⁷⁶
	Pulmonary interstitial emphysema, with one or more of pneumatosis intestinalis, pneumomediastinum, pneumoperitoneum, pneumopericardium, pneumoretroperitoneum, pneumorrhacis, pneumothorax, subcutaneous emphysema, retropharyngeal, paraesophageal air⁴⁹^,¹¹¹^,¹⁶¹^,²³³^,²³⁴^,²³⁵^,²⁷¹^,²⁷⁷^,²⁷⁸^,²⁷⁹^,²⁸⁰^,²⁸¹^,²⁸²^,²⁸³^,²⁸⁴^,²⁸⁵^,²⁸⁶^,²⁸⁷^,²⁸⁸^,²⁸⁹^,²⁹⁰^,²⁹¹^,²⁹²^,²⁹³
	*Rupture of bronchus during bronchoscopy with or without pneumothorax*²⁹⁴^,²⁹⁵
	*Rupture of trachea*²⁸⁷^,²⁹⁶
	Tracheobronchial trauma (eg, bronchitis and bronchial rupture)²³³^,²⁹⁷
	*Transmission of infectious disease*²⁹⁸^,²⁹⁹
Disease transmission	*Transmission of infectious disease*²⁹⁸^,²⁹⁹
Laboratory testing	*False-positive PET scan uptake in muscle related to cough*¹⁰⁷

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Modified from Table 1 in Irwin RS. Complications of cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(suppl1):54S-58S.¹ Complications that are new since 2006 are given in bold italic type.

As noted in 2006,¹ although the pressures, velocities, and energy described earlier, particularly those that relate to the effects on the cardiovascular system, allow coughing to be an effective way of protecting the lungs from near aspiration and aspiration and of providing CPR and arrhythmia control, they can also cause a variety of complications that can be categorized as cardiovascular, constitutional, dermatologic, GI, genitourinary, health-related quality of life, musculoskeletal, neurologic, ophthalmologic, psychosocial, and respiratory.

In planning this update, we followed current CHEST guideline methods⁹ that emphasizes that guidelines should be based on high-quality systematic reviews to address clearly formulated key clinical questions. Because our question was broad and the literature had not been reviewed comprehensively, we chose to conduct a scoping review. A scoping review is based on similar established methods to a systematic review with the intent to clarify working definitions, to identify key concepts, and to establish conceptual boundaries by examining the extent and nature of the evidence.¹⁰^,¹¹ Our specific aims were to (1) systematically identify and thematically categorize the diverse complications of cough providing a guide for future studies and (2) identify gaps in the literature for future research.

Methods

To begin our literature search, we asked the following key clinical question: What are the potential complications associated with the act of coughing that have been reported in infants, children, adolescents and adults? A complication was defined as “a morbid process or event that occurs during the course of a disease that is not an essential part of that disease, although it may result from it or from independent causes.”¹² We considered death to be associated with a complication when the authors of the case report or case series described the death as following the complication of cough and it did not appear to be due to another event. To guide the search of our scoping review, we sought the following elements: population (infants, children, adolescents, and adults), concept (does the study report on the complications as defined earlier secondary to the act of coughing), and context (cough of any duration in patients who are either ambulatory or in the hospital). Inclusion criteria were limited to the English language, cough of any duration, and any study design such as systematic reviews with or without a metaanalysis, diagnostic cohort, case-control study, cross-sectional study, letter to the editor, case reports/series, other reports. Exclusion criterion was a report of an adverse event rather than a complication, unless cough initiated the event. An adverse event was defined as “an incident in which harm resulted to a person receiving health care.”¹³

Search Strategy

A systematic review of the literature was performed. Studies published in PubMed and SCOPUS databases were identified from the beginning of the database to September 6, 2019. Because cough and complication retrieved 13,750 citations in PubMed alone, the search was limited to subject heading. The search strings can be found in e-Appendix 1.

Data Screening and Extraction

Two authors (C. L. F. and R. S. I.) independently analyzed the titles and content of the abstracts to assess inclusion criteria. From the selected titles and abstracts, full reports about potentially relevant studies were obtained, and two authors (C. L. F., N. D., or R. S. I.) independently assessed the eligibility of the studies and completed data extraction. Disagreements were discussed and resolved by consensus. A third author was available to help resolve disagreements if necessary. Even though the screening focused on publications not published in the 2006 guideline, all the articles cited in the 2006 review were reanalyzed. During this re-review of the articles published in the 2006 review, we came across 38 articles that did not appear in the current search.

Results

Literature Study Selection

The process of study selection is outlined in Figure 1, which shows that there were an initial 3,202 unique articles identified by our search string. After being screened, 2,858 abstracts and titles were excluded based on the inclusion and exclusion criteria, which left 344 that underwent full text review. Full text review resulted in the inclusion of 247 articles plus 38 additional citations from the 2006 guideline that were not identified by our search string. The 2006 guideline was also included, which resulted in 286 articles.

Flow diagram of preferred reporting items for study selection. *From Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement*. PLoS Med. *2009;6(7):e1000097. For more information, visitwww.consort-statement.org*.

Complications

The complications associated with cough, as identified by the scoping review, are summarized in Tables 1 and 2. The spectra of complications that are associated with coughing are listed in Table 1 in categories that are primarily organ system based and have been modified only minimally from that previously reported in 2006. The new complications, which were identified by the review, that have been added to the original table are included. Since 2006, three new categories of complications have been identified: ear, nose and throat; disease transmission; and laboratory testing. Those complications that were reported as leading to death are listed in Table 2. A data table (e-Table 1) shows more detail about the complications in the articles from the new search that are categorized and summarized in Tables 1 and 2.

Table 2.

Cough-Associated Complications That Lead to Death

Cough-Associated Complication	Age/Sex	Comorbid Illness	Comment
Death to self and others
Cough syncope in heavy goods-vehicle drivers causing serious traffic accidents resulting in death of two drivers and two pedestrians¹⁹⁰	UA, UA	UA	Cough syncope can lead to death for the drivers and others.
Death to self
Cough associated with spontaneous arterial gas embolism in patient with chronic necrotizing pneumonia, bullae, and brain infarct with death from complications¹⁶⁰	78 y, M	COPD, smoker, chronic Enterobacter cloacae pneumonia, hypertension, atrial fibrillation, type 2 diabetes mellitus, hypothyroidism, dyslipidemia	Spontaneous arterial gas embolism resulted in brain infarcts and air in the cavernous sinuses, which led to death precipitated by coughing in a patient with preexisting chronic necrotizing pneumonia, blebs, and bullae. Proposed mechanism is likely weakened parenchyma that led to bleb rupture with entrainment of air into the pulmonary veins and left heart.
Paroxysms of cough followed by fainting in patients with asthma (four deaths in the series)¹⁷³	UA, M (n = 281); F (n = 9) (N = 290)	Case series included patients with emphysema, bronchitis, TB, asthma, laryngitis, bronchiectasis, pneumoconiosis, sarcoidosis	Death reported as unequivocal cause after post-tussive syncope in four cases, which accounted for 1% mortality rate in the collective series included two in the literature and two personal cases
Fatal rectus sheath hematoma¹⁰²	82 y, F	Polymyositis and related collagen disorders, well controlled with long-term corticosteroids (prednisone 5 mg daily), occult coronary artery disease	Rectus sheath hematoma in one of three patients reported may have been attributed to coughing associated with pneumonia. She was also on thromboprophylaxis with heparin and prednisone for polymyositis. Her course was complicated by a large hematoma, hypotension, and ultimately death.
Cough-induced lung intercostal (8th space) hernia with large abdominal hematoma in patient with COPD exacerbation and death⁴⁹	73 y, M	COPD, total laryngectomy for laryngeal cancer with tracheostomy	Cough-induced intercostal muscle rupture with lung hernia associated with hematoma of the left chest and abdomen, massive subcutaneous emphysema of the left chest and lumbar region in a patient presenting with an exacerbation of COPD that was improving before the coughing insult, which ultimately resulted in death.
Fatal gas cerebral embolism after heavy coughing while using noninvasive ventilation (bilevel positive airway pressure) for fibrotic lung disease¹⁶²	78 y, M	Severe restrictive lung disease due to fibrotic remodeling due to TB, MALT lymphoma	Cerebral air embolism precipitated by episodes of severe coughing that led to catastrophic stroke in a patient presenting with hemoptysis treated with left bronchial artery embolization, on noninvasive positive pressure ventilation and ultimately death due to intractable treatment of resistant cough.
Pneumomediastinum in children with cough with a death²⁸⁶	4 y, M	Measles and pneumonia	In a case series of five patients with severe cough, one patient had refractory cough due to measles, bronchopneumonia that resulted in extensive subcutaneous emphysema, pneumomediastinum that ultimately led to progressive decline and death.
Pneumomediastinum secondary to coughing in an elderly patient with emphysema with death due to complications²⁸⁸	96 y, M	Under custodial care in the geriatrics division	In this case series of three patients, the current patient experienced extensive subcutaneous emphysema and pneumomediastinum after an episode of coughing that resulted in progressive decline and death.
Prolapse of the rectum with spontaneous rupture of the distal colon and evisceration of the small intestine through the anus in an infant after a bout of coughing and death due to complications⁶⁷	4 Mo, F	Low birthweight	Severe bout of coughing putatively resulted in increased abdominal pressure that caused rectal prolapse, spontaneous rupture of visceral colon, and evisceration of the small bowel.
Cough-induced syncope that resulted in death in the setting of cor pulmonale and obstructive lung disease¹⁹⁸	61 y, M	Anthracosilicosis, COPD, cor pulmonale, right ventricle myocardial infarction	Cough exacerbated the existing pulmonary hypertension and cor pulmonale as measured by right heart catheterization which led to hypotension, syncope, and ultimately death due to cardiac arrest.

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F = female; M = male; MALT = mucosal associated lymphoid tissue; UA = unavailable.

Discussion

Reviews of complications of cough have appeared periodically in the medical literature for many years. Prior to and even after 1991, these publications primarily focused on complications of a physical nature.⁴²^,³⁰⁰^,³⁰¹^,³⁰² In 1991, we published a prospective study that involved 108 consecutive and unselected patients who were referred to our Cough Clinic with chronic cough that included the results of qualitative interviews that identified reasons for which these patients sought medical attention.²³⁰ The reasons all related to cough-associated complications; some were physical, and others were of a psychosocial nature such as fearing that something is wrong, exhaustion, life style change, self-consciousness, and/or fearing cancer, AIDS, or TB (Table 3).²³⁰ These results broadened our understanding of the reasons that patients with chronic cough were seeking care and led to the development of our Adverse Cough Outcome Survey²⁵⁴ that eventually led to our development of the first cough quality of life questionnaire, the CQLQ.²⁵⁵ The importance of the development of validated and reliable cough quality of life patient reported outcome questionnaires in the new millennium has now allowed us to assess not only for and quantify the common physical but also for psychosocial complications as summarized in this review.²⁵⁵^,²⁶⁴^,³⁰³^,³⁰⁴

Table 3.

Reasons That Patients With Chronic Cough Seek Medical Attention

Reason	Frequency, %	Most Troublesome, %
Something’s wrong	98	12
Exhaustion	57	17
Self-conscious	55	10
Insomnia	45	4
Lifestyle change	45	12
Musculoskeletal pain^a	44	3
Hoarseness	43	2
Excessive perspiration	42	1
Urinary incontinence^b	39	9
Dizziness	38	0
Fear of cancer	33	11
Headache	32	3
Fear of AIDS or TB	28	11
Retching	21	4
Vomiting	18	1
Nausea	16	0
Anorexia	15	0
Syncope or near syncope	5	0

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Musculoskeletal pain was documented by chest radiography to be due to rib fracture in only one patient.

Urinary incontinence complicated by cough only in women and two men who had undergone prior transurethral prostatectomy.

Reprinted from Irwin RS, Curley FJ. The treatment of cough: a comprehensive review. Chest. 1991;99(6):1477-1484.²³⁰ With permission from Elsevier.

This scoping review has confirmed the psychosocial complications mentioned earlier as well as more broadly identifying physical complications compared with our 2006 report. The physical complications that have been identified, while primarily drawn from case reports and small case series, suggest that coughing can lead to a variety of complications from the relatively minor to those that can be life-threatening or even lead to death. Although the physiologic forces generated by coughing can result in acute and serious injury to an otherwise healthy individual, their effects may be magnified in patients in the following situations, especially when coughing is sustained: compromised by comorbid illnesses or extremes of age; undergoing surgery (eg, ocular) or procedures (eg, bronchoscopy, upper GI endoscopy); recovering from surgery (eg, cardiac or abdominal); and risk from the side-effects of medications (eg, corticosteroids or anticoagulants). Until definitive studies show the way forward, we speculate that it makes physiologic sense that, whenever possible, attempts to control coughing should be made before surgery to avoid wound dehiscence (eg, sternal or abdominal) or extrusion of ocular contents during eye surgery. This review also raises awareness of potential injury to self and others from uncontrolled coughing during automobile driving.

Our study was a scoping review and not a full systematic review; as such, we were able to identify a multitude of complications of cough and to categorize them for future study. The gap in the literature that this review identified is that we do not know how frequent all the complications are or the strength of their association with cough. However, until future research prospectively provides us with the answer, we are left to speculate about the frequency of some of the more common and/or most troublesome complications of chronic cough in those who presented to a Cough Clinic. For example, in our 1991 prospective study that was cited earlier, the frequency of different categories of complications were tabulated (Table 3).²³⁰ This table suggested that musculoskeletal adverse events that included rib fracture occurred in 44%, syncopal or near-syncopal events in 5%, and urinary incontinence, primarily in women, in 39%. It is interesting to note that another prospective study of ours, published 26 years later in 2017,⁸⁷ with the use of the CQLQ, replicated the urinary incontinence finding of the 1991 study in that urinary incontinence, primarily in women, was cough-associated in 38.8% of subjects. Because of the importance of urinary incontinence in women, and especially women with cough,³⁰⁵ it is important to know that the CQLQ is the only commonly used cough quality of life instrument in research studies that specifically asks about this complication.³⁰⁶

Methodologic Considerations

As noted in the Methods section, our initial literature search returned 13,750 citations in PubMed alone. In reviewing the titles and abstracts of this large volume of literature, we noted a complex and heterogeneous nature of the data (eg, variety of complications, diversity of system affected, diversity of nature of evidence, and a diverse origin of the publications by specialty and country). Based on these findings, it was our opinion that the medical community and patients would be best served by our conducting a scoping review, with the intention of clarifying the conceptual boundaries for the next step of study of complications of cough. This was accomplished by identifying key concepts (actual complications) within the research area and by thematically categorizing them to clarify the working definition of complications of cough. Although this review has identified a multitude of potential complications of cough, we were not attempting to quantify the findings or to make recommendations that go beyond facilitating clinician awareness of the multitude and potential serious nature of the various complications and the importance of following the best available evidence for controlling cough. Because most of the complications were gleaned from case reports and small case series, it is possible that some of the complications occurred coincidentally with cough rather than being caused by coughing. That is the reason that we have used the term, associated with coughing, throughout this review. By thematically categorizing the large number of cough complications, we have provided an outline so that future studies of each system or each complication can be conducted. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications.

Although ours is not the only recent review of the complications that are associated with cough,³⁰⁷ it is the only one that has followed current established methods,¹⁰^,¹¹ which is similar to a systemic review because it is transparent, systematic, and replicable.³⁰⁸ This methodologic rigor makes our review different from both our 2006 publication¹ and the more recent review.³⁰⁷

In summary, clinicians should not underestimate the impact of coughing to patients due to the potential for serious and life-threatening complications to themselves or to others and the adverse effect on quality of life. It is not an inconsequential problem or concern and should not be trivialized. As noted by Banyai and Joannides,³⁰¹ in their 1956 seminal review that addressed cough hazards, “the assessment of cough can be made only in light of its possible advantages and harmful implications” and “obviously, there is an urgent need for greater awareness of the potential damage of cough so as to accomplish its satisfactory treatment as well as to prevent its serious sequelae.” Therefore, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications associated with coughing.³⁰⁹^,³¹⁰ Additionally, clinicians should also make sure that patients are made aware of the potential unintended consequences of not following recommendations that are intended to ameliorate cough. The myriad complications that can occur from cough indicate the need both for further study and for aggressive treatment of cough when it occurs.

Acknowledgments

Author contributions: All authors had full access to all the data in the study; therefore, all take responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. R. S. I. sered as the principal author. C. L. F. and N. D. contributed substantially to the study design, data analysis, and interpretation, and the writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. S. I. and C. L. F., as co-developers of the Cough Quality of Life Questionnaire, report that they hold the copyright of this patient-reported outcome measure that is mentioned in this review. None declared (N. D.).

∗CHEST Expert Cough Panel Collaborators: Abd Moain Abu Dabrh, MBBCh, MS (Mayo Clinic, Jacksonville, FL); Kenneth W. Altman, MD, PhD (Geisinger Commonwealth School of Medicine, Danville, PA); Elie Azoulay, MD, PhD (University of Paris, Paris, France); Alan F. Barker, MD (Oregon Health & Science University, Portland, OR); Surinder S. Birring, MBChB, MD (Division of Asthma, Allergy and Lung Biology, King’s College London, Denmark Hill, London, United Kingdom); Donald C. Bolser, PhD, and Louis-Philippe Boulet, MD, FCCP (Institut universitaire de cardiologie et de pneumonlogie de Québec, Quebec, [IUCPQ], QC, Canada); Sidney S. Braman, MD, FCCP (Mount Sinai Hospital, New York, NY); Christopher Brightling, MBBS, PhD, FCCP (University of Leicester, Glenfield Hospital, Leicester, United Kingdom); Brendan Canning, PhD (Johns Hopkins Asthma and Allergy Center, Baltimore, MD); Anne B. Chang, MBBS, PhD, MPH (Royal Children’s Hospital, Queensland, Australia); Terrie Cowley (The TMJ Association, Milwaukee, WI); Paul Davenport, PhD (Department of Physiological Sciences, University of Florida, Gainesville, FL); Ali A. El Solh, MD, MPH (University at Buffalo, State University of New York, Buffalo, NY); Patricio Escalante, MD, FCCP (Mayo Clinic, Rochester, MN); Stephen K. Field, MD (University of Calgary, Calgary, AB, Canada); Dina Fisher, MD, MSc (University of Calgary, Respiratory Medicine, Calgary, AB, Canada); Cynthia T. French, PhD, FCCP (UMass Memorial Medical Center, Worcester, MA); Cameron Grant, MB ChB, PhD (University of Aukland, New Zealand); Susan M. Harding, MD, FCCP (Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL); Anthony Harnden, MB ChB, MSc (University of Oxford, Oxford, England); Adam T. Hill, MB ChB, MD (Royal Infirmary and University of Edinburgh, Edinburgh, Scotland); Richard S. Irwin, MD, Master FCCP (UMass Memorial Medical Center, Worcester, MA); Vivek Iyer, MD, MPH Mayo Clinic, Rochester MN); Peter J. Kahrilas, MD (Feinberg School of Medicine, Northwestern University, Chicago, IL); Joanne Kavanagh, MBChB (Division of Asthma, Allergy and Lung Biology, King’s College London); Denmark Hill, London, United Kingdom); Karina A. Keogh, MD (Mayo Clinic, Rochester, MN); Kefang Lai, MD, PhD (First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China); Andrew P. Lane, MD (Johns Hopkins University School of Medicine, Baltimore, MD); Kaiser Lim, MD (Mayo Clinic, Rochester, MN); J. Mark Madison, MD, FCCP (UMass Memorial Medical Center, Worcester, MA); Mark A. Malesker, PharmD, FCCP (Creighton University School of Pharmacy and Health Professions, Omaha, NE); Stuart Mazzone, PhD, FCCP (University of Melbourne, Victoria, Australia); Lorcan McGarvey, MD (The Queens University Belfast, Belfast, United Kingdom); Alex Molasoitis, PhD, RN (Hong Kong Polytechnic University, Hong Kong, China); Abigail Moore, BM BCh (University of Oxford, Oxford, England); M. Hassan Murad, MD, MPH (Mayo Clinic, Rochester, MN); Peter Newcombe, PhD (School of Psychology University of Queensland, QLD, Australia); John Oppenheimer, MD (UMDNJ-Rutgers University); Bruce Rubin, MEngr, MD (Virginia Commonwealth University, Richmond, VA); Richard J. Russell, MBBS (University of Leicester, Glenfield Hospital, Leicester, United Kingdom); Jay H. Ryu, MD, FCCP (Mayo Clinic, Rochester, MN); Sonal Singh, MD, MPH (UMass Memorial Medical Center, Worcester, MA); Jaclyn Smith, MB ChB, PhD (University of Manchester, Manchester, England); Susan M. Tarlo, MBBS, FCCP (Toronto Western Hospital, Toronto, ON, Canada); Anne E. Vertigan, PhD, BAppSc (SpPath) (John Hunter Hospital, NSW, Australia).

Other contributions: We thank Nancy Harger, MLS, clinical service librarian who works in the University of Massachusetts Medical School Library, Worcester, MA, who undertook all the searches for this systematic review.

Additional information: The e-Appendix and e-Table can be found in the Supplemental Materials section of the online article.

Footnotes

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Contributor Information

Richard S. Irwin, Email: Richard.Irwin@umassmemorial.org.

CHEST Expert Cough Panel:

Abd Moain Abu Dabrh, Kenneth W. Altman, Elie Azoulay, Alan F. Barker, Surinder S. Birring, Donald C. Bolser, Louis-Philippe Boulet, Sidney S. Braman, Christopher Brightling, Brendan Canning, Anne B. Chang, Terrie Cowley, Paul Davenport, Ali A. El Solh, Patricio Escalante, Stephen K. Field, Dina Fisher, Cynthia T. French, Cameron Grant, Susan M. Harding, Anthony Harnden, Adam T. Hill, Richard S. Irwin, Vivek Iyer, Peter J. Kahrilas, Joanne Kavanagh, Karina A. Keogh, Kefang Lai, Andrew P. Lane, Kaiser Lim, J. Mark Madison, Mark A. Malesker, Stuart Mazzone, Lorcan McGarvey, Alex Molasoitis, Abigail Moore, M. Hassan Murad, Peter Newcombe, John Oppenheimer, Bruce Rubin, Richard J. Russell, Jay H. Ryu, Sonal Singh, Jaclyn Smith, Susan M. Tarlo, and Anne E. Vertigan

Supplementary Data

e-Online Data

mmc1.pdf^{(450.1KB, pdf)}

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PERMALINK

Life-Threatening and Non-Life-Threatening Complications Associated With Coughing

Richard S Irwin, MD, Master FCCP

Natasha Dudiki, MD

Cynthia L French, PhD, FCCP

Abstract

Background

Research Question

Study Design and Methods

Results

Interpretation

Table 1.

Methods

Search Strategy

Data Screening and Extraction

Results

Literature Study Selection

Figure 1.

Complications

Table 2.

Discussion

Table 3.

Methodologic Considerations

Acknowledgments

Footnotes

Contributor Information

Supplementary Data

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

Life-Threatening and Non-Life-Threatening Complications Associated With Coughing

Richard S Irwin, MD, Master FCCP

Natasha Dudiki, MD

Cynthia L French, PhD, FCCP

Abstract

Background

Research Question

Study Design and Methods

Results

Interpretation

Table 1.

Methods

Search Strategy

Data Screening and Extraction

Results

Literature Study Selection

Figure 1.

Complications

Table 2.

Discussion

Table 3.

Methodologic Considerations

Acknowledgments

Footnotes

Contributor Information

Supplementary Data

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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