Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Effects of bepotastine, a nonsedating H1-antihistamine, for the treatment of persistent cough and allergic rhinitis: a randomised, double-blind, placebo-controlled trial.

Background: Empirical therapy with oral histamine-1 receptor antagonists (H1RAs) is often used for patients with suspected upper airway cough syndrome. No placebo-controlled trials with nonsedating H1RAs (nsH1RAs) have evaluated validated cough outcomes. The objective of the present study was to assess the effect of an nsH1RA, bepotastine, on cough outcomes in patients with allergic rhinitis and persistent cough. Methods: A randomised, double-blind, placebo-controlled trial was conducted. Adult patients with persistent cough (>3 weeks in duration) and symptomatic allergic rhinitis were recruited and randomly assigned to receive either bepotastine or placebo at a 1:1 ratio. The primary outcome was cough-specific quality of life assessed using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included cough severity visual analogue scale (VAS), throat VAS, Cough Hypersensitivity Questionnaire, Sinonasal Outcome Test-22 score and drug adverse events. Results: Between October 2021 and September 2022, 50 participants (43 females; mean age 46.28 years; median cough duration 3 months) were assigned to either the bepotastine 10 mg twice daily or placebo group in a 1:1 ratio. After 2 weeks of treatment, both bepotastine and placebo groups showed significant improvements in the LCQ scores, but there was no significant difference in the magnitude of change between the groups (3.45±2.10 versus 3.04±2.94, p=0.576). Secondary outcomes were also comparable. Conclusions: Despite the relatively small sample size, our study clearly demonstrated that a 2-week treatment with bepotastine did not provide therapeutic benefits for cough outcomes. These findings suggest against the use of nsH1RAs with the intention of improving cough outcomes, even in patients with persistent cough and allergic rhinitis.

Feasibility and Utility of a Smartphone Application-Based Longitudinal Cough Monitoring in Chronic Cough Patients in a Real-World Setting.

PURPOSE: This study evaluated the feasibility and utility of longitudinal cough frequency monitoring with the Hyfe Cough Tracker, a mobile application equipped with cough-counting artificial intelligence algorithms, in real-world patients with chronic cough. METHODS: Patients with chronic cough (> 8-week duration) were monitored continuously for cough frequency with the Hyfe app for at least one week. Cough was also evaluated using the Leicester Cough Questionnaire (LCQ) and daily cough severity scoring (0-10). The study analyzed adherence rate, the correlation between objective cough frequency and subjective scores, day-to-day variability, and patient experience. RESULTS: Of 65 subjects consecutively recruited, 43 completed the study. The median cough monitoring duration was 13.9 days, with a median adherence of 91%. Study completion was associated with baseline cough severity, and the adherence rate was higher in younger subjects. Cross-sectional correlation analyses showed modest correlations between objective and subjective cough measures at the group level. However, in time series correlation analyses, correlations between objective and subjective measures widely varied across individuals. Cough frequency had greater day-to-day variability than daily cough severity scores in most subjects. A patient experience survey found that 70% of participants found the cough monitoring helpful, 86% considered it acceptable, and 84% felt it was easy to use. CONCLUSION: Monitoring cough frequency longitudinally for at least one week may be feasible. The substantial day-to-day variability in objective cough frequency highlights the need for continuous monitoring. Grasping the implications of daily cough variability is crucial in both clinical practice and clinical trials.

Codeine prescription pattern and treatment responses in patients with chronic cough: a routinely collected institutional database analysis.

Background: Codeine has been long used as an antitussive drug in several countries. However, a prescription pattern of codeine, such as dose or treatment duration, has not been reported in detail. Furthermore, there is few scientific evidence on the efficacy and safety. We aimed to examine codeine prescription pattern and explore treatment response in patients with chronic cough in real-world practice. Methods: This was a retrospective cohort analysis of patients with chronic cough who were newly referred to tertiary allergy and asthma clinics between July 2017 and July 2018. Routinely collected electronic healthcare records (EHRs), including medical notes, prescriptions, and outpatient visits, were analyzed. Codeine prescription records were examined for duration, mean daily dose, and 1-year cumulative dose. Codeine responses were evaluated by manual EHR reviews. Results: Among a total of 1,233 newly referred patients with chronic cough, 666 were prescribed codeine for a median [interquartile range (IQR)] of 27.5 days (IQR 14-60 days); the median daily dose was 30 mg/year (IQR 21.6-30 mg/year), and the 1-year cumulative dose was 720 mg/year (IQR 420-1,800 mg/year). About 14.0% of patients were prescribed codeine for >8 weeks; they were older and had a longer cough duration, throat abnormal sensation and less dyspnea than patients prescribed codeine for ≤8 weeks or who did not receive codeine. Codeine prescription and duration was positively associated with the number of other cough-related medications, diagnostic tests, or outpatient visits. Cough status change was noted in 61.3% of codeine-prescribed patients (as 'improved' in 40.1% and 'not improved' in 21.2%), but not documented in 38.7%. Side effects were described in 7.8%. Conclusions: Codeine prescription may be frequent and chronic in real-world practice of patients with chronic cough, despite the lack of robust clinical evidence on the efficacy. High prescription rates suggest unmet clinical needs. Prospective studies are warranted to identify codeine treatment responses and safety, and to build up clinical evidence to guide appropriate use of narcotic antitussives.

Clinical Characteristics of Post-COVID-19 Persistent Cough in the Omicron Era.

Cough is one of the most common symptoms of acute coronavirus disease 2019, but cough may persist for weeks or months. This study aimed to examine the clinical characteristics of patients with post-coronavirus disease (COVID) persistent cough in the Omicron era. We conducted a pooled analysis comparing 3 different groups: 1) a prospective cohort of post-COVID cough (> 3 weeks; n = 55), 2) a retrospective cohort of post-COVID cough (> 3 weeks; n = 66), and 3) a prospective cohort of non-COVID chronic cough (CC) (> 8 weeks; n = 100). Cough and health status was assessed using patient-reported outcomes (PROs). Outcomes, including PROs and systemic symptoms, were longitudinally evaluated in the prospective post-COVID cough registry participants receiving usual care. A total of 121 patients with post-COVID cough and 100 with non-COVID CC were studied. Baseline cough-specific PRO scores did not significantly differ between post-COVID cough and non-COVID CC groups. There were no significant differences in chest imaging abnormality or lung function between groups. However, the proportions of patients with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb were 44.7% in those with post-COVID cough and 22.7% in those with non-COVID CC, which were significantly different. In longitudinal assessment of the post-COVID registry (n = 43), cough-specific PROs, such as cough severity or Leicester Cough Questionnaire (LCQ) scores, significantly improved between visits 1 and 2 (visit interval: median 35 [interquartile range, IQR: 23-58] days). In the LCQ score, 83.3% of the patients showed improvement (change ≥ +1.3), but 7.1% had worsened (≤ -1.3). The number of systemic symptoms was median 4 (IQR: 2-7) at visit 1 but decreased to median 2 (IQR: 0-4) at visit 2. In summary, post-COVID persistent cough was similar in overall clinical characteristics to CC. Current cough guideline-based approaches may be effective in most patients with post-COVID cough. Measurement of FeNO levels may also be useful for cough management.

Long-COVID severe refractory cough: discussion of a case with 6-week longitudinal cough characterization.

Long coronavirus disease (COVID) refers to an array of variable and fluctuating symptoms experienced after acute illness, with signs and symptoms that persist for 8-12 weeks and are not otherwise explicable. Cough is the most common symptom of acute COVID-19, but cough may persist in some individuals for weeks or months after recovery from acute phase. Long-COVID cough patients may get stigmatised because of the public fear of contagion and reinfection. However, clinical characteristics and longitudinal course of long-COVID cough have not been reported in detail, and evidence-based treatment is also lacking. In this paper, we describe a case of long-COVID severe refractory cough with features of laryngeal hypersensitivity and dysfunction. We characterized cough using patient-reported outcomes and engaged in continuous cough frequency monitoring. Through the case study, we discuss potential mechanisms, managements, and clinical implications of long-COVID refractory cough problems.

Highly Conductive PEDOT:PSS Films with 1,3-Dimethyl-2-Imidazolidinone as Transparent Electrodes for Organic Light-Emitting Diodes.

Highly conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) films as transparent electrodes for organic light-emitting diodes (OLEDs) are doped with a new solvent 1,3-dimethyl-2-imidazolidinone (DMI) and are optimized using solvent post-treatment. The DMI doped PEDOT: PSS films show significantly enhanced conductivities up to 812.1 S cm(-1) . The sheet resistance of the PEDOT: PSS films doped with DMI is further reduced by various solvent post-treatment. The effect of solvent post-treatment on DMI doped PEDOT: PSS films is investigated and is shown to reduce insulating PSS in the conductive films. The solvent posttreated PEDOT: PSS films are successfully employed as transparent electrodes in white OLEDs. It is shown that the efficiency of OLEDs with the optimized DMI doped PEDOT: PSS films is higher than that of reference OLEDs doped with a conventional solvent (ethylene glycol). The results present that the optimized PEDOT: PSS films with the new solvent of DMI can be a promising transparent electrode for low-cost, efficient ITO-free white OLEDs.