The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI - 0.22; 0.88), 0.31 (CI - 1.74; 2.35), 0.32 (CI - 0.29; 0.93) and 0.34 (CI - 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI - 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Gastroesophageal reflux disease (GERD) as a possible cause of chronic cough is known for decades. However, more than 75% of patients with extraoesophageal symptoms do not suffer from typical symptoms of GERD like pyrosis and regurgitations and have negative upper gastrointestinal endoscopy. For such a condition term laryngopharyngeal reflux (LPR) was introduced and is used for more than two decades. Since the comprehensive information on relationship between chronic cough and LPR is missing the aim of this paper is to summarize current knowledge based on review of published information during last 13 years. Laryngopharyngeal reflux is found in 20% of patients with chronic cough. The main and recognized diagnostic method for LPR is 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, revealing reflux episodes irritating the upper and lower respiratory tract mucosa. The treatment of LPR should be initiated with dietary and lifestyle measures, followed by proton pump inhibitor (PPI) therapy and other measures. Despite progress, more research is needed for accurate diagnosis and targeted therapies. Key areas for exploration include biomarkers for diagnosis, the impact of non-acid reflux on symptom development, and the efficacy of new drugs. Further studies with a focused population, excluding other causes like asthma, and using new diagnostic criteria for LPR are essential. It\'s crucial to consider LPR as a potential cause of unexplained chronic cough and to approach diagnosis and treatment with a multidisciplinary perspective.

UNASSIGNED: Chronic cough is a frequent reason for seeking consultation with primary care providers. The recent widespread adoption of virtual care offers a promising alternative that can be used to optimize the assessment and management of this condition. The objective of this review was to map and identify the strategies used to assess and/or manage chronic cough virtually, and to explore their impact on cough severity and patient satisfaction with virtual care.
UNASSIGNED: A scoping review was conducted in MEDLINE, EMBASE, and CINAHL in May 2023. Research questions were defined based on the Population, Concept, Context mnemonic, and literature search was conducted using a three-step approach. Study selection involved the steps of identification, screening, eligibility, and inclusion. A descriptive synthesis was performed, and quantitative variables were presented as absolute and relative frequencies.
UNASSIGNED: A total of 4953 studies were identified and seven met the inclusion criteria. The following mHealth and telehealth strategies were identified: diagnostic website, specialized online clinic, online speech language therapy, and remote follow-up to assess the effectiveness of in-person interventions. Results indicated that these virtual strategies can be useful to assess chronic cough, treat, and track chronic cough symptoms. Overall, patients were satisfied with the approaches.
UNASSIGNED: Although literature is scarce, evidence suggests that virtual strategies for the assessment and management of chronic cough may be effective and are well-received by patients. However, further research is needed to identify the type and characteristics of virtual approaches leading to optimize and facilitate the care of patients with this condition. This will also help develop a strong body of evidence to support their incorporation into guidelines and clinical practice.

BACKGROUND: Refractory or unexplained chronic cough (RCC or UCC) is difficult to manage and is usually treated by the off-label use of drugs approved for other indications.
OBJECTIVE: The objectives of this systematic literature review (SLR) were to identify and characterize the current published body of evidence for the efficacy and safety of treatments for RCC or UCC.
METHODS: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The SLRs pre-defined population included patients ≥18 years of age who were diagnosed with chronic cough. The review was not restricted to any intervention type or study comparator, nor by timeframe.
RESULTS: A total of 20 eligible publications from 19 unique trials were included. Seventeen of these trials were randomized controlled trials and most (14/17) were placebo-controlled. There was considerable variability between trials in the definition of RCC or UCC, participant exclusion and inclusion criteria, outcome measurement timepoints, and the safety and efficacy outcomes assessed. Several trials identified significant improvements in cough frequency, severity, or health-related quality of life measures while participants were on treatment, although these improvements did not persist in any of the studies that included a post-treatment follow-up timepoint.
CONCLUSIONS: In the absence of an approved therapy, placebo remains the most common comparator in trials of potential RCC or UCC treatments. The between-study comparability of the published evidence is limited by heterogeneity of study design, study populations, and outcomes measures, as well as by concerns regarding study size and risk of bias.

BACKGROUND: When patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough.
METHODS: Based on Arksey and O\'Malley\'s scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included.
RESULTS: Among 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies.
CONCLUSIONS: In future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

OBJECTIVE: Chronic cough (CC), defined as a cough persisting ≥ 8 weeks, can have a substantial negative impact on health-related quality of life (HRQoL). This is exacerbated by challenges with timely diagnosis and a lack of approved therapies. A systematic literature review (SLR) was conducted to identify evidence on HRQoL and health state utility values associated with refractory CC or unexplained CC.
METHODS: Electronic database searches were supplemented with searches of conference proceedings and health technology assessment body websites. Two independent reviewers assessed all citations for inclusion based on predefined inclusion/exclusion criteria. Key inclusion criteria were patient populations with CC and reporting of patient-reported outcomes or utilities using generic or disease-specific measures.
RESULTS: Following screening, 65 studies were identified for inclusion in the SLR. Of these, 23 studies assessed HRQoL among patients with CC who were not treated or treated with unspecified interventions, and 42 studies in patients who were treated with specified interventions. The studies indicated a substantial decrement to HRQoL as a result of CC, characterized by generic and disease-specific patient-reported outcome measures. HRQoL was impacted across multiple domains, including physical, psychological, and social functioning. The studies also demonstrated the potential for treatments to have a significant positive impact on HRQoL.
CONCLUSIONS: CC can substantially affect HRQoL in patients, across physical, psychological, and social domains. Although treatments can improve HRQoL in these patients, the available evidence is limited. There remains an unmet need for approved pharmacological treatments to alleviate CC and improve HRQoL for these patients.

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Tracheobronchopathia osteochondroplastica (TO) is an orphan disease of the tracheobronchial tree without any known etiological attributes. There are several case reports published on this condition, yet the available information about the TO is discrete and of little clinical value. This scoping review is the first large-scale review on TO that collates individual patient data from the published case reports and descriptively analyses the clinicopathological features of this unique condition along with its management approaches and therapeutic outcomes. The objective was to synthesize comprehensive literature review on TO that can aid clinical practice and further research. An electronic search conducted in five large databases, including PubMed, EMBASE, CINAHL, CENTRAL, and Web of Science, for the published articles of TO yielded 1072 items. After screening, the individual patient data of 371 TO cases from 228 eligible articles were included and analysed in this scoping review.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12070-023-03998-6.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.