A cohort description and analysis of the effect of gabapentin on idiopathic cough

BACKGROUND: Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms. METHODS: A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words ‘cough’ and ‘gabapentin’ in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire. RESULTS: We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms. Responders had a higher pre-treatment cough severity score (p=0.02) and were more likely to have a history of pre-cough airway infection (p=0.04). Current cough severity score negatively correlated with the Leicester Cough Questionnaire scores (p=0.05). CONCLUSION: Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection

The impact of therapeutics on mortality in hospitalised patients with COVID-19:systematic review and meta-analyses informing the European Respiratory Society living guideline

Hospitalised patients with coronavirus disease 2019 (COVID-19) have a high mortality rate. There are an increasing number of published randomised controlled trials for anti-inflammatory, anti-viral and other treatments. The European Respiratory Society Living Guidelines for the Management of Hospitalised Adults with COVID-19 were published recently, providing recommendations on appropriate pharmacotherapy.Patient, Intervention, Comparator and Outcomes questions for key interventions were identified by an international panel and systematic reviews were conducted to identify randomised controlled trials meeting the inclusion criteria. The importance of end-points were rated, and mortality was identified as the key "critical" outcome for all interventions. Random-effects meta-analysis was used to pool studies and provide effect estimates for the impact of treatments on mortality.Corticosteroids, hydroxychloroquine, azithromycin, remdesivir, anti-interleukin (IL)-6 monoclonal antibodies, colchicine, lopinavir/ritonavir and interferon-β have been reviewed.Our results found further evidence in support of the use of corticosteroids, particularly dexamethasone, and anti-IL-6 receptor monoclonal antibody therapy. These data support the need to identify additional therapies with beneficial effects on mortality

A comprehensive approach to lung function in bronchiectasis

Background: International guidelines recommend simple spirometry for bronchiectasis patients. However, pulmonary pathophysiology of bronchiectasis is very complex and still poorly understood. Our objective was to characterize lung function in bronchiectasis and identify specific functional sub-groups. Methods: This was a multicenter, prospective, observational study enrolling consecutive adults with bronchiectasis during stable sate. Patients underwent body-plethysmography before and after acute bronchodilation testing, diffusing lung capacity (DLCO) with a 3-year follow up. Air trapping and hyperinflation were a residual volume (RV) > 120%predicted and a total lung capacity>120%predicted. Acute reversibility was: \u394FEV1 6512% and 200 mL from baseline (FEV1rev) and \u394RV 6510% reduction from baseline (RVrev). Sensitivity analyses included different reversibility cutoffs and excluded patients with concomitant asthma or chronic obstructive pulmonary disease. Results: 187 patients were enrolled (median age: 68 years; 29.4% males). Pathophysiological abnormalities often overlapped and were distributed as follows: air trapping (70.2%), impaired DLCO (55.7%), airflow obstruction (41.1%), hyperinflation (15.7%) and restriction (8.0%). 9.7% of patients had normal lung function. RVrev (17.6%) was more frequent than FEV1rev (4.3%). Similar proportions were found after multiple sensitivity analyses. Compared with non-reversible patients, patients with RVrev had more severe obstruction (mean(SD) FEV1%pred: 83.0% (24.4) vs 68.9% (26.2); P = 0.02) and air trapping (RV%pred, 151.9% (26.6) vs 166.2% (39.9); P = 0.028). Conclusions: Spirometry alone does not encompass the variety of pathophysiological characteristics in bronchiectasis. Air trapping and diffusion impairment, not airflow obstruction, represent the most common functional abnormalities. RVrev is related to worse lung function and might be considered in bronchiectasis\u2019 workup and for patients\u2019 functional stratification

The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation:A case-crossover analysis

In bronchiectasis, exacerbations are believed to be triggered by infectious agents, but often no pathogen can be identified. We hypothesised that acute air pollution exposure may be associated with bronchiectasis exacerbations.We combined a case-crossover design with distributed lag models in an observational record linkage study. Patients were recruited from a specialist bronchiectasis clinic at Ninewells Hospital, Dundee, UK.We recruited 432 patients with clinically confirmed bronchiectasis, as diagnosed by high-resolution computed tomography. After excluding days with missing air pollution data, the final model for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM; 10; ) was based on 6741 exacerbations from 430 patients and for nitrogen dioxide (NO; 2; ) it included 6248 exacerbations from 426 patients. For each 10 µg·m; -; ³ increase in PM; 10; and NO; 2; , the risk of having an exacerbation that same day increased significantly by 4.5% (95% CI 0.9-8.3) and 3.2% (95% CI 0.7-5.8) respectively. The overall (lag zero to four) increase in risk of exacerbation for a 10 μg·m; -3; increase in air pollutant concentration was 11.2% (95% CI 6.0-16.8) for PM; 10; and 4.7% (95% CI 0.1-9.5) for NO; 2; Subanalysis showed higher relative risks during spring (PM; 10; 1.198 (95% CI 1.102-1.303), NO; 2; 1.146 (95% CI 1.035-1.268)) and summer (PM; 10; 2.142 (95% CI 1.785-2.570), NO; 2; 1.352 (95% CI 1.140-1.602)) when outdoor air pollution exposure would be expected to be highest.In conclusion, acute air pollution fluctuations are associated with increased exacerbation risk in bronchiectasis

Clinical phenotypes in adult patients with bronchiectasis

Bronchiectasis is a heterogeneous disease. This study aimed at identifying discrete groups of patients with different clinical and biological characteristics and long-term outcomes. This was a secondary analysis of five European databases of prospectively enrolled adult outpatients with bronchiectasis. Principal component and cluster analyses were performed using demographics, comorbidities, and clinical, radiological, functional and microbiological variables collected during the stable state. Exacerbations, hospitalisations and mortality during a 3-year follow-up were recorded. Clusters were externally validated in an independent cohort of patients with bronchiectasis, also investigating inflammatory markers in sputum. Among 1145 patients (median age 66 years; 40% male), four clusters were identified driven by the presence of chronic infection with Pseudomonas aeruginosa or other pathogens and daily sputum: "Pseudomonas" (16%), "Other chronic infection" (24%), "Daily sputum" (33%) and "Dry bronchiectasis" (27%). Patients in the four clusters showed significant differences in terms of quality of life, exacerbations, hospitalisations and mortality during follow-up. In the validation cohort, free neutrophil elastase activity, myeloperoxidase activity and interleukin-1\u3b2 levels in sputum were significantly different among the clusters. Identification of four clinical phenotypes in bronchiectasis could favour focused treatments in future interventional studies designed to alter the natural history of the disease

Bronchiectasis Rheumatoid Overlap Syndrome Is an Independent Risk Factor for Mortality in Patients With Bronchiectasis:A Multicenter Cohort Study

BACKGROUND: This study assessed if bronchiectasis (BR) and rheumatoid arthritis (RA), when manifesting as an overlap syndrome (BROS), were associated with worse outcomes than other BR etiologies applying the Bronchiectasis Severity Index (BSI). METHODS: Data were collected from the BSI databases of 1,716 adult patients with BR across six centers: Edinburgh, United Kingdom (608 patients); Dundee, United Kingdom (n = 286); Leuven, Belgium (n = 253); Monza, Italy (n = 201); Galway, Ireland (n = 242); and Newcastle, United Kingdom (n = 126). Patients were categorized as having BROS (those with RA and BR without interstitial lung disease), idiopathic BR, bronchiectasis-COPD overlap syndrome (BCOS), and "other" BR etiologies. Mortality rates, hospitalization, and exacerbation frequency were recorded. RESULTS: A total of 147 patients with BROS (8.5% of the cohort) were identified. There was a statistically significant relationship between BROS and mortality, although this relationship was not associated with higher rates of BR exacerbations or BR-related hospitalizations. The mortality rate over a mean of 48 months was 9.3% for idiopathic BR, 8.6% in patients with other causes of BR, 18% for RA, and 28.5% for BCOS. Mortality was statistically higher in patients with BROS and BCOS compared with those with all other etiologies. The BSI scores were statistically but not clinically significantly higher in those with BROS compared with those with idiopathic BR (BSI mean, 7.7 vs 7.1, respectively; P < .05). Patients with BCOS had significantly higher BSI scores (mean, 10.4), Pseudomonas aeruginosa colonization rates (24%), and previous hospitalization rates (58%). CONCLUSIONS: Both the BROS and BCOS groups have an excess of mortality. The mechanisms for this finding may be complex, but these data emphasize that these subgroups require additional study to understand this excess mortality