Is fractional exhaled nitric oxide a treatable trait in chronic cough: a narrative review.

Background and Objective: Current management of chronic cough is largely based on sequential therapeutic trials. The concept of treatable traits was first introduced for individualized treatment of chronic airway diseases; however, it has emerged as a potentially useful strategy in revising the management of chronic cough. This narrative review aimed to analyze the literature to determine if fractional exhaled nitric oxide (FeNO) is a treatable trait in chronic cough, compared to other type 2 biomarkers, and to summarize current knowledge and gaps in the clinical application. Methods: An online electronic search was performed on PubMed, Web of Science, and Scopus of English-language literature with following keywords: cough, nitric oxide (NO), eosinophils, biomarker, and treatable trait. Relevance and eligibility of each article were assessed by one or more of the authors and a narrative review was composed. Key Content and Findings: Eosinophilic or type 2 airway inflammation is a major treatable trait in patients with chronic cough. Induced sputum tests are regarded as the gold standard for defining inflammatory phenotype, however, technically demanding and cannot be widely applied in clinical practice. FeNO, a practical biomarker, has emerged as an alternative to induced sputum analyses. Mechanistic and clinical evidence indicated that FeNO had a potential for diagnostic utility and treatment response predictability. Conclusions: FeNO measurement may help to identify patients with chronic cough that will benefit from corticosteroid treatment. Further studies are warranted to determine the diagnostic roles of FeNO in the management of patients with chronic cough.

Recurrent Cough in the Elderly: A Forgotten Entity.

INTRODUCTION: Recurrent cough is little researched in adults. We investigated the prevalence, risk factors, and consequences of recurrent cough, and compared the results to those of isolated chronic cough. METHODS: Cross-sectional email survey in an elderly community-based population. Recurrent cough was defined as ≥ 3 cough episodes within one year (each lasting ≥ 1 week) and no current chronic cough. Isolated chronic cough was defined as current cough lasting ≥ 8 weeks and no recurrent cough. RESULTS: The prevalence of recurrent cough was 3.8% among all respondents (n = 5983). Recurrent cough was associated with asthma (aOR 3.32 (95% CI 2.13-5.18)), chronic rhinosinusitis (2.91 (1.89-4.46)), family history of chronic cough (2.59 (1.88-3.56)), analgesic intolerance (2.13 (1.27-3.57)), male gender (1.92 (1.39-2.66)), gastro-esophageal reflux disease (1.73 (1.21-2.47)), obstructive sleep apnoea (1.69 (1.23-2.32)), symptom sum (1.12 per symptom (1.03-1.22)), and younger age (0.96 per year (0.93-1.00)). Isolated chronic cough was associated with chronic rhinosinusitis (3.45 (2.39-4.97)), asthma (2.17 (1.38-3.41), gastro-esophageal reflux disease (1.80 (1.32-2.47)), family history of chronic cough (1.80 (1.35-2.41)), obstructive sleep apnoea (1.49 (1.12-2.00)), symptom sum (1.18 per symptom (1.10-1.27)), and body mass index (0.96 per unit (0.93-1.00)). Among subjects with recurrent and isolated chronic cough, the prevalence of depressive symptoms were 7.7% and 4.2%, p = 0.11, the Leicester Cough Questionnaire total scores 15.2 (14.6-15.8) and 16.3 (16.0-16.6), P = 0.001, and the mean number of yearly cough-related doctor`s visits 0.58 (0.45-0.71) and 0.36 (0.19-0.53), P = 0.007, respectively. CONCLUSION: The risk factors and consequences of recurrent and isolated chronic cough were comparable. Recurrent cough seems beneficial to address in cough evaluation.

Healthcare-Seeking Behaviour Due to Cough in Finnish Elderly: Too Much and Too Little.

INTRODUCTION: Cough-related healthcare-seeking has not been studied specifically in the elderly, although chronic cough is most prevalent among them. We studied the frequencies and predictors of any (≥ 1) and repeated (≥ 3) doctor's visits due to any cough episode during the past year, and due to the current cough episode. METHODS: This was a cross-sectional email survey among a Finnish community-based elderly population. Participants with current cough and age ≥ 64 years were included in the analyses (n = 1109). RESULTS: The proportions of participants with ≥ 1 and ≥ 3 cough-related doctor's visits during the past year were 25.9% and 7.1%, respectively. Repeated visitors accounted for 55.9% of the visits during the past year. These visits first increased with cough duration but decreased after 5 years. In the multivariate analysis, bronchiectasis [aOR 3.22 (CI95% 1.08-9.58)], asthma [2.62 (1.56-4.40)], chronic sputum production [1.61 (0.94-2.76)], low self-assessed health status [1.40 (1.04-1.88)] and Leicester Cough Questionnaire total score [1.34 per tertile (1.10-1.62)] predicted repeated cough-related doctor's visits during the past year. The proportions of ≥ 1 and ≥ 3 doctor's visits due to current cough were 31.8% and 15.5%, respectively. Among participants with current chronic cough, 60.1% had not visited a doctor. CONCLUSION: A minority of participants accounted for most of the cough-related doctor's visits during the past year, whereas most participants with chronic cough had never sought medical help for it. The heavy healthcare users were not those with the longest cough episodes. Repeated visitors due to cough were characterised by chronic phlegmy respiratory conditions, and quality-of-life impairment.

Cough in the Elderly During the COVID-19 Pandemic.

INTRODUCTION: The prevalence of chronic cough increases with age. However, data on the prevalence and background disorders of cough subtypes in the elderly are scarce. The objective of this study was to identify the point prevalence and risk factors of acute, subacute, and chronic cough in an elderly community-based population. METHODS: This was a cross-sectional email survey amongst 26,205 members of the Finnish Pensioners' Federation during the COVID-19 pandemic in spring 2021. RESULTS: The response rate was 23.6% (6189). 5983 subjects aged at least 64 years were included in the analyses (mean 72.6 years, 66.3% female). The point prevalence of daily acute, subacute, and chronic cough were 1.4%, 0.7%, and 9.6%, respectively. Only 0.4% of the subjects had a COVID-19 infection. In the multivariate analyses, chronic rhinosinusitis, and obstructive sleep apnoea were common risk factors for all cough subtypes. Chronic cough had several risk factors; Bronchiectasis (OR 5.79 (CI95% 2.70-12.41)), current asthma (2.67 (2.02-3.54)), chronic rhinosinusitis (2.51 (1.94-3.24)), somatic symptom score (1.13 per symptom (1.07-1.19)), family history of chronic cough (1.88 (1.54-2.30)), gastro-oesophageal reflux disease (1.86 (1.50-2.32)), advanced age (1.20 per decade (1.02-1.40)), chronic obstructive pulmonary disease (1.74 (0.99-3.05)), dog ownership (1.42 (1.07-1.89)), and obstructive sleep apnoea (1.41 (1.16-1.73)). CONCLUSION: Acute and subacute cough, as well as previous COVID-19 infection, were uncommon in this Finnish elderly population. The prevalence of chronic cough was higher than that previously found in younger adults. Chronic cough is a multifactorial disorder in the elderly.

Utility of Cough Provocation Tests in Chronic Cough and Respiratory Diseases: A Comprehensive Review and Introduction of New Reference Ranges for the Capsaicin Test.

Cough provocation tests (CPTs) are an objective measurement of the sensitivity of the cough reflex arc. However, they are not established in clinical practice because a large variability of response in healthy subjects limits their diagnostic value. There is a paucity of studies that have investigated CPT reference ranges in healthy subjects. This systematic review describes the variability of the responses to CPTs in healthy subjects and factors that influence it. A new analysis of 134 healthy subjects was conducted to create reference ranges for single-breath capsaicin CPT by calculating the interquartile ranges for the provocative concentration of capsaicin to induce 2 and 5 coughs. Female subjects had a more sensitive cough reflex than male counterparts. The ability of CPTs to distinguish various respiratory diseases from healthy subjects was also reviewed. Cough sensitivity was consistently heightened in the following groups: unselected patients with chronic, refractory, or recurrent cough, unexplained chronic cough, gastro-esophageal reflux-associated cough, cough-variant asthma, lower airway symptoms induced by chemical irritants, and fibrotic interstitial lung diseases. In the following groups, hypersensitivity of the cough reflex was present in those individuals whose symptom profile was predominated by cough: asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and sarcoidosis. In the following conditions, patients usually cough in order to expectorate mucus from their airways, not because of a hypersensitive cough reflex arc: productive cough, asthma, upper airway cough syndrome, COPD, bronchiectasis, cystic fibrosis, and chronic respiratory infections. CPTs have the potential to identify patients with chronic respiratory symptoms due to cough reflex hypersensitivity, thereby providing a targeted approach for therapy.

Neurotrophins in chronic cough: association with asthma but not with cough severity.

BACKGROUND AND AIMS: Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels. METHODS: Serum and sputum levels of nerve growth factor (NGF), serum levels of brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were analyzed by enzyme immunoassay in 19 healthy subjects and 47 patients with chronic cough. In addition, cough sensitivity to hypertonic saline was assessed, cough diary was kept, Leicester Cough Questionnaire was filled in, peak flow was monitored and spirometry, skin prick tests, exhaled nitric oxide measurement and histamine challenge were performed. RESULTS: The NGF levels did not differ between the healthy subjects and the patients with chronic cough and were not associated with any index describing cough severity. However, these levels in both serum (P = 0.01) and sputum (P = 0.025) samples were associated with asthma. There was a statistically significant association between serum and sputum NGF levels (R = 0.45, P = 0.026). The serum BDNF levels did not differ between the groups and were not associated with any of the background characteristics. The serum NT-3 levels were below the detection limit in most subjects and therefore these data were not analyzed. CONCLUSIONS: Neither chronic cough nor its severity is associated with abnormal neurotrophin levels. High NGF levels among some patients with chronic cough may indicate a presence of asthma.

Cold air-provoked respiratory symptoms: the mechanisms and management.

OBJECTIVES: To describe the mechanisms and management of cold air-provoked respiratory symptoms. STUDY DESIGN: A literature review. METHODS: The review includes human epidemiological studies, human and animal experimental studies, as well as human studies about management of the cold air-provoked respiratory symptoms. RESULTS: Cold air is unlikely to be a causal factor initiating respiratory diseases but a symptom trigger. In the present review, the airway responses beyond these symptoms were divided into three types. The short-term responses are those that develop within minutes in response to sudden cooling of the airways. Subjects with asthma or rhinitis are especially prone to these responses. The long-term responses are those that develop in response to repeated and long-standing cooling and drying of the airways, usually in endurance athletes. Finally, there are the physiological, reflex-mediated lower-airway responses to cooling of the skin or upper airways. CONCLUSIONS: The mechanisms beyond cold air-provoked respiratory symptoms vary considerably and mainly depend on the individual's susceptibility and the ventilation level during the cold exposure. An understanding of these mechanisms is essential for successful management of the symptoms.