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– Overview of the evaluation of chronic cough in an adult. ACE-I: angiotensin converting enzyme inhibitor; PEF: peak expiratory flow; PNDS: post-nasal drip syndrome; GORD: gastro-oesophageal reflux disease.
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... for further investigation ( fig. 1). The smoking history and the quantity and character of sputum (if any) should be detailed in full. Chronic cough in cigarette smokers is dose-related [1] and may be productive of mucoid or mucopurulent secretions as a result of chronic bronchitis, or may be dry, as a result of the irritant effects of cigarette smoke. Examination may ...
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... Однако в настоящей главе будут обсуждаться препараты, провоцирующие проявление этого симптома без каких-либо морфологических изменений в дыхательной системе. Хронический кашельшироко известный побочный эффект при приеме иАПФ, частота его возникновения в этом случае, по опубликованным данным, достигает 5-35% [33]. Интересно, что кашель чаще развивается у пациентов, получающих терапию иАПФ при острой сердечной недостаточности, чем у пациентов, принимающих те же лекарства при артериальной гипертензии. ...
В настоящем издании, составленном с учетом актуальных клинических рекомендаций, рассматриваются вопросы клиники, диагностики и лечения основных заболеваний респираторной системы. Руководство предназначено для повышения квалификации широкого круга врачей: терапевтов, пульмонологов, фтизиатров, аллергологов и иммунологов, онкологов, хирургов, оториноларингологов, педиатров, инфекционистов, патологоанатомов и представителей смежных специальностей. Также издание адресовано студентам старших курсов медицинских вузов, ординаторам, аспирантам и может быть использовано в качестве учебника для подготовки к практическим занятиям и итоговой государственной аттестации.
... The international consensus defines cough based on duration, with acute cough lasting up to 8 weeks and chronic cough exceeding 8 weeks [25] . Prolonged cough may be related to persistent lung inflammation from various etiologies, such as chronic obstructive pulmonary disease, bronchial asthma, and cough variant asthma [26] . This sustained inflammation is hypothesized to deplete energy and cause fatigue. ...
Objective
Chronic fatigue syndrome (CFS) is a prevalent symptom of post-coronavirus disease 2019 (COVID-19) and is associated with unclear disease mechanisms. The herbal medicine Qingjin Yiqi granules (QJYQ) constitute a clinically approved formula for treating post-COVID-19; however, its potential as a drug target for treating CFS remains largely unknown. This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.
Methods
This prospective cohort analysis included 4,212 adults aged ≥65 years who were followed up for 7 years with 435 incident CFS cases. Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS. A proteome-wide, two-sample Mendelian randomization (MR) analysis was employed to explore the proteins associated with the identified causal factors of CFS, which may serve as potential drug targets. Furthermore, we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.
Results
Among 4,212 participants (47.5% men) with a median age of 69 years (interquartile range: 69–70 years) enrolled in 2004, 435 developed CFS by 2011. Causal graph analysis with multivariate logistic regression identified frequent cough (odds ratio: 1.74, 95% confidence interval [CI]: 1.15–2.63) and insomnia (odds ratio: 2.59, 95% CI: 1.77–3.79) as novel causal factors of CFS. Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule (ESAM) was causally linked to both chronic cough (odds ratio: 1.019, 95% CI: 1.012–1.026, P = 2.75 e ⁻⁰⁵ ) and insomnia (odds ratio: 1.015, 95% CI: 1.008–1.022, P = 4.40 e ⁻⁰⁸ ) in CFS. The major bioactive compounds of QJYQ, ginsenoside Rb2 (docking score: −6.03) and RG4 (docking score: −6.15), bound to ESAM with high affinity based on virtual screening.
Conclusions
Our integrated analytical framework combining epidemiological, genetic, and in silico data provides a novel strategy for elucidating complex disease mechanisms, such as CFS, and informing models of action of traditional Chinese medicines, such as QJYQ. Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.
... For instance, GREM2, a gene involved in developmental processes 23, is also associated with allopurinol efficacy 24 . and MME, implicated in neuropeptide degradation 25 and associated with ACE inhibitor-induced cough 26 , were amongst the uniquely predicted genes. Lastly variants in COL26A1 have been associated to Aspirin-intolerant asthma. ...
Gene imputation and TWAS have become a staple in the genomics medicine discovery space; helping to identify genes whose regulation effects may contribute to disease susceptibility. However, the cohorts on which these methods are built are overwhelmingly of European Ancestry. This means that the unique regulatory variation that exist in non-European populations, specifically African Ancestry populations, may not be included in the current models. Moreover, African Americans are an admixed population, with a mix of European and African segments within their genome. No gene imputation model thus far has incorporated the effect of local ancestry (LA) on gene expression imputation. As such, we created LA-GEM which was trained and tested on a cohort of 60 African American hepatocyte primary cultures. Uniquely, LA-GEM include local ancestry inference in its prediction of gene expression. We compared the performance of LA-GEM to PrediXcan trained the same dataset (with no inclusion of local ancestry) We were able to reliably predict the expression of 2559 genes (1326 in LA-GEM and 1236 in PrediXcan). Of these, 546 genes were unique to LA-GEM, including the CYP3A5 gene which is critical to drug metabolism. We conducted TWAS analysis on two African American clinical cohorts with pharmacogenomics phenotypic information to identity novel gene associations. In our IWPC warfarin cohort, we identified 17 transcriptome-wide significant hits. No gene reached are prespecified significance level in the clopidogrel cohort. We did see suggestive association with RAS3A to P2RY12 Reactivity Units (PRU), a clinical measure of response to anti-platelet therapy. This method demonstrated the need for the incorporation of LA into study in admixed populations.
... Traditionally, conditions such as asthma, chronic bronchitis, and laryngeal dysfunction have been associated with chronic cough in adults [8]. However, it is essential to recognize that not all patients with these conditions develop chronic cough. ...
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed during the incomplete combustion of organic substances, such as coal and oil. PAHs exposure is known to increase the incidence of respiratory diseases; however, limited research has focused on their impact on chronic cough. In this study, we utilized data from the National Health and Nutritional Examination Surveys (NHANES) from 2003 to 2012. Chronic cough was defined as 'coughing most days for three consecutive months or more'. Employing survey-weighted multivariate logistic regression models, we identified positive associations between all six PAHs metabolites (1-NAP, 2-NAP, 3-FLU, 2-FLU, 1-PHE, and 1-PYR) found in urine and the presence of chronic cough. Furthermore, results from restricted cubic spline modeling revealed a nonlinear relationship between urinary levels of 1-NAP, 2-NAP, 3-FLU, 2-FLU, and 1-PYR and the risk of chronic cough. Co-exposure modeling unveiled the combined effects of multiple exposures and the relative contributions of each PAHs. Notably, co-exposure to PAHs was positively associated with an increased risk of chronic cough, where 2-FLU emerged as the primary contributor to this association. These findings were particularly pronounced in individuals with high cotinine exposure (≥0.05 ng/mL). In conclusion, this study presents epidemiological evidence linking PAHs exposure to an elevated risk of chronic cough. Further prospective investigations are warranted to corroborate these findings.
... Open access an estimated lifetime risk (in those born after 1960) of 3% in males and 2% in females (Cancer Research UK). 1 A third of individuals diagnosed with RCC have stage 4 cancer at presentation with spread to the lungs, brain, bone and liver and thus can present with a persistent cough, haemoptysis, abnormal liver function tests and bone pain, among other symptoms (Kidney Cancer UK). 2 Chronic cough affects 10% of the adult population and is a common reason why patients visit their general practitioner (GP). 3 In half of the patients, a cause (eg, asthma, bronchiectasis, gastro-oesophageal reflux and medication) is identified, but in the remainder, no cause is found. The recognition of cough occurring in patients with RCC was first described in 1935 by Creevy,4 and Estafan and Walsh, in a review of symptom prevalence in 1000 patients with cancer, found that cough was present in 31% of patients with RCC. 5 Even now, clinicians treating patients with cough or RCC remain unaware of this association. ...
Introduction:
Cough as a symptom of renal cell carcinoma (RCC) was first described by Creevy in 1935, and despite one (unpublished) study suggesting it may affect 31% of these patients, as well as cough being discussed in forums for patients with kidney cancer, few clinicians are aware of this association. The cough has been described as unusual in nature, resolving rapidly after treatment with nephrectomy/embolisation but returning if the tumour recurs.
Methods and analysis:
A prospective study using a questionnaire will identify the prevalence of cough in patients with suspected or confirmed RCC attending the Specialist Centre for Kidney Cancer (London, UK). A longitudinal study in a representative sample of these patients, using EQ-5D-5L and Leicester Cough Questionnaires, together with the use of semi-structured interviews with patients, will identify the impact of cough in addition to having a diagnosis of suspected or confirmed RCC on quality of life. To investigate cough mechanisms, a pilot study using cough hypersensitivity testing will be performed on patients with RCC, with and without a cough. Clinical samples (urine, blood, phlegm and breath condensate) from patients with RCC, with and without a cough, will be collected and analysed for the presence of substances known to trigger or enhance cough and compared with the results obtained from healthy volunteers.
Ethics and dissemination:
Ethical approval has been granted (UK HR REC 22/PR/0791 dated 25/08/2022). Study outputs will be presented and published nationally and internationally at relevant conferences. This study will establish the prevalence of cough in patients with suspected or confirmed kidney cancer and support the education of clinicians to consider this diagnosis in patients with chronic cough (eg, recommending protocols to include both kidneys when investigating respiratory symptoms with chest CT scans). If substances known to trigger or enhance cough are identified and elevated in clinical samples, this research could offer potential targets for treatment for this distressing symptom.
Trial registration number:
NIHR CRN portfolio CPMS ID:53 372.
... It is prevalent and can affect the quality of life in patients (2)(3)(4). Anatomic diagnostic protocols, which aim to identify and treat the causes of cough according to the neuroanatomy of relevant reflex pathways, are key principles in managing patients with chronic cough (5)(6)(7). However, certain aspects of the approach are lacking. ...
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.
... Although cough is an important defense mechanism that protects the airway from foreign bodies and clears excessive secretions, it can cause discomfort and impair the patients' quality of life, especially when it becomes chronic [2,3]. Identifying the cause of chronic cough can be difficult because it may be multifactorial, and causative symptoms such as postnasal drip or gastroesophageal reflux are often clinically silent [4]. ...
Although cough is a common respiratory symptom, determining its cause is challenging. We aimed to explore how cough severity and characteristics vary with different etiologies, while investigating their interrelations with demographic features. Adult patients (n = 220) with chronic cough and completed diagnostic work-up and the COugh Assessment Test were enrolled. A correlation network analysis was used to examine the associations between the demographic features and cough severity/characteristics across various etiologies such as upper airway cough syndrome, asthma, eosinophilic bronchitis, gastroesophageal reflux disease (GERD), and idiopathic cough. Demographic features like age and sex showed complex associations with cough characteristics and severity. Cough severity decreased with age, especially in cases of eosinophilic bronchitis and GERD. Women with eosinophilic bronchitis reported more severe cough, while men with idiopathic cough reported more severe cough. Asthma was significantly linked to more sleep disturbance and fatigue, independent of age and sex, whereas GERD showed less sleep disturbance and fatigue. Network analysis revealed overall close associations between cough characteristics, though hypersensitivity in asthma and sleep disturbance in GERD were not linked with other cough traits. In conclusion, the demographic features and cough characteristics were interrelated, exhibiting distinct patterns based on the etiology.
... Chronic cough is a type of cough that exists every day with a duration of more than four weeks. [1,2] Passive smoking is the exposure to tobacco smoke of a nonsmoking person through close contact or by sharing a common household. [2] In the literature, instead of passive smoking, the terms 'exposure of environmental tobacco smoke (ETS)' , 'second-hand smoking' , 'involuntary smoking' , and 'exposure of side stream smoke' are commonly used. ...
... [2] In the literature, instead of passive smoking, the terms 'exposure of environmental tobacco smoke (ETS)' , 'second-hand smoking' , 'involuntary smoking' , and 'exposure of side stream smoke' are commonly used. [1] There is a growing amount of evidence concerning significant harms on respiratory system health about the exposure to ETS for children. [3][4][5] It has been reported that sharing the household with especially smoking mothers, related to the number of cigarettes smoked per day; causes recurrent respiratory system infections, wheezing, and chronic cough starting from early infancy. ...
Bacground: Our study was planned to reveal the objective relation between urine cotinine level and tobacco smoke exposure in children suffering from chronic cough. Methods: Between ages 5-18 years, 58 patients with chronic cough with no underlying specific cause and 54 healthy individuals were included in the study. Results: There was a statistically significant difference between urine cotinine levels of cases those who exposed and unexposed (based on the declaration of parents) to tobacco smoke (p
... 1,2 Chronic cough can be triggered by acute respiratory virus infection and can occur as a symptom of other chronic conditions including asthma and gastroesophageal reflux disease. [1][2][3][4] The prevalence of chronic cough in adults in the United Kingdom and other countries has not been accurately determined. A meta-analysis published in 2015 estimated the overall prevalence of chronic cough in European countries as 12.7%. ...
Background
Chronic cough, defined as daily cough for at least 8 weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the United Kingdom.
Methods
Study participants were general population respondents to the 2018 United Kingdom National Health and Wellness Survey. Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matching on age, gender, and the modified Charlson Comorbidity Index.
Results
Of 15,000 respondents, 715 reported chronic cough in the previous 12 months and 918 during their lifetime associated with age and smoking history. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence at 6.2%. Chronic cough correlated with higher rates of severe anxiety and depression in the past two weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents had visited a healthcare provider in the past 6 months than respondents without chronic cough (p<0.001) with a mean of 5.8 and 3.7 visits per respondent, respectively (p<0.001).
Conclusion
Adults with chronic cough report lower quality of life which was associated with lost work productivity and greater healthcare resource utilisation.
... The frequency and severity of cough provide useful information for the diagnosis of upper respiratory diseases and the evaluation of their treatments. 1 Conventionally, cough has been assessed manually, using methods such as cough visual analog scores and a diary scorecard. 2 However, these methods have the limitation of being subjective. ...
Cough is a protective mechanism of the proximal respiratory tract. The frequency and severity of cough provide useful information for the diagnosis of upper respiratory diseases and the evaluation of their treatments. Manual cough classification is subjective, labor-intensive, and time-consuming. In this study, a cough classification technique based on a microelectromechanical system microphone is proposed. For the classification process, various tabular and time-series machine learning algorithms were applied, and their results were compared. With respect to the time-series algorithms, the random interval decision tree, random interval spectral forest, and random convolution kernel transform (ROCKET) methods were used. With respect to the tabular algorithms, a convolution neural network (CNN) with 40 Mel-frequency cepstral coefficients (MFCCs) and a recurrent neural network with 40 MFCCs were used. Voluntary cough and noncough (throat clearing, expiration, speaking, and rest) signals were recorded from 10 healthy subjects. The ROCKET method showed the best accuracy (98.40%). In addition, while its training took the longest time (1628.80 s), this algorithm took a reasonably short time for prediction (0.27 s). The CNN showed the second-best accuracy (97.81%) with short training (454.13 s) and prediction (0.40 s) times. Thus, given its accuracy and prediction time, the ROCKET method is recommended for this type of classification over the CNN algorithm. To validate the application of the proposed methods, two methods were applied to a public Coswara data set. To classify one cough class and three non-cough classes, the ROCKET and CNN showed reasonable accuracies of 90.33% and 89.16%, respectively.
