The Influence of Gender on Cough Reflex Sensitivity

doi:10.1378/chest.113.5.1319

Chest

Volume 113, Issue 5, May 1998, Pages 1319-1321

https://doi.org/10.1378/chest.113.5.1319 Get rights and content

Background

The more common occurrence in women of cough due to angiotensin-converting enzyme inhibitors raises the possibility of gender-related differences in the sensitivity of the cough reflex. Of two recent studies that evaluated cough response to inhaled capsaicin in normal subjects, one demonstrated heightened sensitivity of the cough reflex in women compared with men, while the other revealed no gender-related differences. To further investigate this question, we reviewed our experience with cough challenge testing in normal volunteers.

Study objective

To compare cough reflex sensitivity in healthy adult female and male subjects.

Design

Retrospective data analysis.

Setting

Academic medical center.

Participants

One hundred healthy volunteers (50 male, 50 female).

Interventions

Subjects inhaled capsaicin in ascending, doubling concentrations until the concentration inducing five or more coughs (C₅) was reached. In addition, the concentration inducing two or more coughs (C₂; cough threshold) was measured.

Results

Mean log C₅ was significantly lower in women than in men: 1.02±0.09 (SEM) μM vs 1.41±0.08 μM, respectively (p=0.002). Log C₂ (cough threshold) was also significantly lower in female subjects: 0.534±0.068 μM vs 0.870±0.065 μM in male subjects (p=0.00058).

Conclusion

Healthy women have a more sensitive cough reflex than do healthy men. The reasons for this significant gender difference remain to be elucidated, but may involve a heightened sensitivity, in women, of the sensory receptors within the respiratory tract that mediate cough.

Section snippets

Subjects

Data from all healthy volunteers who underwent capsaicin cough challenge testing in our laboratory between November 1995, and May 1997, were used in the present analysis. The study group included subjects who had participated in several recent investigations requiring the measurement of a baseline cough threshold. Subjects granted informed consent for studies in which they participated. Protocols were approved by our hospital's Institutional Review Board. All subjects were healthy, adult

RESULTS

Data from 100 subjects were available for analysis: 50 women (mean age 31.9±4.9 [SD] years; range, 22 to 44 years), and 50 men (mean age 30.8±3.8 years; range, 26 to 41 years). Induction of five coughs (C₅) was achieved in all subjects. The distribution of C₅ values is displayed in Figure 1. Mean log C₅ among female subjects was 1.02±0.09 (SEM) μM, significantly lower than that of male subjects, 1.41 ±0.08 μM (p=0.002; Fig 2). Cough threshold (log C₂) in women was also significantly lower than

DISCUSSION

We have demonstrated a heightened sensitivity of the cough reflex to inhaled capsaicin in women compared with men of similar age. Our results confirm the findings of Fujimura et al,⁶ who reported lower capsaicin cough thresholds in both young and middle-aged women compared with age-matched men. The investigators of that study delivered capsaicin aerosol via a tidal breathing method for 15 s, whereas we employed a single-breath inhalation, from functional residual capacity to total lung

REFERENCES (9)

DicpinigaitisPV et al.
Antitussive effect of the GABA-agonist baclofen
Chest
(1997)
WiddicombeJG.
Neurophysiology of the cough reflex
Eur Respir J
(1995)
OsI et al.
Female preponderance for lisinopril-induced cough in hypertension
Am J Hypertens
(1994)
CoulterDM et al.
Cough associated with captopril and enalapril
BMJ
(1987)

There are more references available in the full text version of this article.

Cited by (152)

Global Physiology and Pathophysiology of Cough: Part 2. Demographic and Clinical Considerations: CHEST Expert Panel Report
2021, Chest
Citation Excerpt :
Cough as a side-effect of angiotensin converting enzyme inhibitor therapy is more common in women than men.33 Cough hypersensitivity is more prevalent in adult women and can be demonstrated experimentally with an increased cough response to inhaled capsaicin not only among adult women with chronic cough,18,20 but also in healthy adult women.34,35 The clinical features that characterize cough hypersensitivity are more prevalent in adult women with chronic cough.
Cough characteristics vary between patients, and this can impact clinical diagnosis and care. The purpose of part two of this state-of-the-art review is to update the American College of Chest Physicians (CHEST) 2006 guideline on global physiology and pathophysiology of cough.
A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 using prespecified search terms.
We describe the demographics of typical patients with cough in the clinical setting, including how cough characteristics change across age. We summarize the effect of common clinical conditions impacting cough mechanics and the physical properties of mucus on airway clearance.
This is the second of a two-part update to the 2006 CHEST cough guideline; it complements part one on basic phenomenology of cough by providing an extended clinical picture of cough along with the factors that alter cough mechanics and efficiency in patients. A greater understanding of the physiology and pathophysiology of cough will improve clinical management.
Animal models of cough
2021, Respiratory Physiology and Neurobiology
Cough is a vital airway reflex that keeps the respiratory tract wisely protected. It is also a sign of many diseases of the respiratory system and it may become a disease in its own right. Even though the efficacy of antitussive compounds is extensively studied in animal models with promising results, the treatment of pathological cough in humans is insufficient at the moment. The limited translational potential of animal models used to study cough causes, mechanisms and possible therapeutic targets stems from multiple sources. First of all, cough induced in the laboratory by mechanical or chemical stimuli is far from natural cough present in human disease.
The main objective of this review is to provide a comprehensive summary of animal models currently used in cough research and to address their advantages and disadvantages. We also want to encourage cough researchers to call for precision is research by addressing the sex bias which has existed in basic cough research for decades and discuss the role of specific pathogen-free (SPF) animals.
Prevalence of Arnold nerve reflex in subjects with and without chronic cough: Relevance to Cough Hypersensitivity Syndrome
2019, Pulmonary Pharmacology and Therapeutics
Cough is induced by stimulation of structures innervated by the vagus nerve, including the upper and lower airways and distal esophagus. The Arnold nerve reflex describes cough resulting from stimulation of the external auditory canal, which is innervated by the auricular branch of the vagus. We have recently reported the increased prevalence of this reflex in adults, but not children, with chronic cough, relative to healthy adult and pediatric subjects. The prevalence of the Arnold nerve reflex in patients with pulmonary disease but without chronic cough has not been investigated previously.
Three hundred adults and 100 children with chronic cough, 50 adults with stable pulmonary disease but without chronic cough, as well as 100 adult and 100 pediatric volunteers, underwent evaluation consisting of stimulation of the external auditory canal of each ear with a cotton-tipped applicator. Cough occurring within 10 s of stimulation was considered induced by the intervention.
Arnold's nerve reflex was present in 23.3% of adults and 3% of children with chronic cough. The prevalence of the reflex was 2% among healthy adults and children. In adults with chronic cough, Arnold's nerve reflex was observed more commonly in women (29.3%) than men (10.5%), and was unilateral in the majority of patients (88.6%). In patients with respiratory disease but without chronic cough, Arnold nerve reflex was present in 2%.
The greater than 11-fold prevalence of the Arnold nerve reflex in adults with chronic cough compared with healthy volunteers and adults with respiratory disease but without chronic cough, supports the concept of the Cough Hypersensitivity Syndrome (CHS), in which vagal hypersensitivity is proposed to underlie chronic refractory cough. The absence of increased prevalence among children with chronic cough suggests that CHS is an acquired condition, perhaps triggered by viral respiratory infection or other environmental factor.
Non-pharmacological techniques for the extremes of the cough spectrum
2018, Respiratory Physiology and Neurobiology
Cough can be viewed as a continuum where extremes represent disease phenotypes. Under this unified concept, non-pharmacological treatment for the extremes of the cough spectrum includes both cough augmentation and cough control techniques. Supporting the cough motor output and exercising the cognitive control on coughing are the main directions of these techniques. Cough augmentation can be provided to patients who present low ability to generate adequate peak cough flows, with the aim to develop the sheering forces that are essential for effective airway clearance. On the other hand, individuals with high cough sensitivity or frequency can practice techniques for cough control, which incorporates a combination of education, retraining and psychological support. These techniques aim to empower patients to increase their supramedulary control on cough. Although hypotheses that are generated by the physiology of cough can support most non-pharmacological techniques, their exact mechanisms of effectiveness remain unclear.
The double-sidedness of cough in the elderly
2018, Respiratory Physiology and Neurobiology
Citation Excerpt :
Capsaicin cough sensitivity was similar between boys and girls in pre-pubertal or early pubertal ages, but significantly higher in late pubertal girls than in boy counterparts (Varechova et al., 2008). In a study of young healthy adult volunteers (n = 100, age range: 22–44 years), capsaicin cough response was also significantly more sensitive in females than in males (Dicpinigaitis and Rauf, 1998). In studies of adult patients with chronic cough (mostly older adults), cough sensitivity (determined by C2 or C5 induced by capsaicin or citric acid inhalation) was more pronounced in females than in males (Kastelik et al., 2002; Song et al., 2014).
Cough is a physiological reflex to protect airways against aspiration, but also it is one of the most frequent problems that lead patients to seek medical care. Chronic cough is more prevalent in the elderly than younger subjects, and more challenging to manage due to frequent comorbidities and possible side effects from drug treatment. Meanwhile, cough reflex does not decrease with natural aging but is often impaired by pathologic conditions like stroke. The impairment in cough reflex may lead to fatal complication like aspiration pneumonia. In this paper, we reviewed epidemiology and clinical considerations for chronic cough in the elderly, and summarized aging-related changes in cough reflex and also possible ways to normalize cough reflex and prevent aspiration pneumonia.
Sensitivity of airway cough-related afferents is influenced by female sex hormones
2018, Respiratory Physiology and Neurobiology
Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen – E2 and progesterone – Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin.

View all citing articles on Scopus

: Supported by a grant from the American Lung Association of New York.

View full text

Chest

Clinical Investigations: MiscellaneousThe Influence of Gender on Cough Reflex Sensitivity

Background

Study objective

Design

Setting

Participants

Interventions

Results

Conclusion

Section snippets

Subjects

RESULTS

DISCUSSION

Chest

Neurophysiology of the cough reflex

Eur Respir J

Female preponderance for lisinopril-induced cough in hypertension

Am J Hypertens

Cough associated with captopril and enalapril

BMJ

Clinical Investigations: Miscellaneous
The Influence of Gender on Cough Reflex Sensitivity