Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma.

BACKGROUND: Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA. METHODS: Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 µg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis. RESULTS: The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05). CONCLUSIONS: Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

[Chinese national guideline on diagnosis and management of cough(2021)].

Advances have been made in the diagnosis, management and pathogenesis of chronic cough in recent years. To better present the current progress achieved both in China and abroad, the Asthma Group of Chinese Thoracic Society organized experts from various disciplines, including respiratory medicine, gastroenterology, reflux surgery, otorhinolaryngology, pediatrics and traditional Chinese medicine, to update the Chinese national guideline on diagnosis and management of cough(2015). In this new version of guideline, previous evidence quality and recommendation strength were re-evaluated and updated, meanwhile some new recommendations were added, and certain previous recommendations were deleted. In general, the basic structure of the latest version remained the same as the previous version, which includes definitions, epidemiology and pathogenesis of chronic cough, investigations, evaluations of chronic cough, diagnosis and management of acute cough, subacute cough and chronic cough, and empirical and symptomatic treatment of chronic cough, etc.

Chronic cough: new insights and future prospects.

Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2-18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed.

The Relationship between Aeroallergen Sensitization and Chronic Cough in School-Aged Children from General Population.

OBJECTIVE: Determining sensitivity to allergens is an essential step in diagnosing children with allergic diseases. Chronic cough has remained poorly understood with causative triggers. The purpose of our study was to shed light on the relationship between sensitization to aeroallergens and chronic cough. METHODS: This population-based study examined children (aged 7 years to 13 years) between June and July 2016. The 1,259 children, 72 of whom (5.7%) had a chronic cough, and 1,187 of whom (94.3%) did not (controls), completed the questionnaire, but 1,051 children completed skin prick tests (SPTs) with eight aeroallergens. RESULTS: There were positive SPT results to at least 1 allergen in 549 children (52.2%). Sensitization to house dust mite (HDM) was most common (chronic cough = 46.9%; controls = 47.2%), followed by pollen (chronic cough = 21.9%; controls = 16.5%) in both groups, but there was no difference in allergic profile and sensitization to aeroallergen (P > 0.05 for all comparisons). Multivariable analysis with adjustment for confounding indicated that children who were in sensitization to pollen had an increased risk of chronic cough (aOR = 2.387; 95% CI: 1.115 to 5.111; P = 0.025). Multivariable analysis with adjustment for confounding indicated that children who were exposed to current smoking (aOR = 4.442; 95% CI: 1.831 to 10.776; P = 0.001) and mold (aOR = 1.988; 95% CI: 1.168 to 3.383; P = 0.011) were associated with chronic cough. CONCLUSION: Sensitization to pollen should be considered as a potential contributing factor to the development of chronic cough in school-aged children.

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components.

Objective Assessment of Cough: An Early Marker of Response to Biological Therapies in Asthma?

Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (p < 0.02). Significant improvements were also observed in mean ACQ score (3-1.6, p < 0.01) and exacerbation frequency (5.5 per year - 1.3, p < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.

Micronutrients as immunomodulatory tools for COVID-19 management.

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.

A 55-Year-Old Man With Cough and Hematochezia.

CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Do clinical investigations predict long-term wheeze? A follow-up of pediatric respiratory outpatients.

INTRODUCTION: The contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear. AIM: We performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma. METHODS: We studied children aged 6 to 16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnea, or cough in 2007. The initial assessment included spirometry, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up 7 years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression. RESULTS: At baseline, 111 children were examined in 2007. After 7 years, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio, 4.2; 95% CI, 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence. CONCLUSION: Reported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.

The evaluation ofefficacy and safety of Cough (EMA) granules used for upper respiratory disorders.

Ivy leaf is used for the treatment of respiratory diseases with the intensive mucus formation, respiratory infections, and irritating cough coming from the common cold. Conferring to clinical trials, the efficacy, and tolerability of ivy leaf is good. The main compounds accountable for biological activity are triterpene and saponins. Ivy leaves show convulsive/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic and anti-thrombin activity. Not only ivy but also marshmallow and mustard seeds are used for these indications. This study was conducted to evaluate the efficacy and safety of Cough (EMA; European Medicines Agency) granules used for upper respiratory disorders. This clinical trial was conducted on 150 patients, out of which 75received the Cough (EMA) granules and 75received the placebo. The age range of patients was 3 years to above 15 years. The sample paired t-test was applied to evaluate the significant level. Cough (EMA) granules were found effective in the treatment of cough, cold, and flu symptoms. The new treatment Cough (EMA) granules were safe and well tolerated in patient at given specific age group. The study recommends that Cough (EMA) granules can be used effectively in the treatment of upper respiratory tract infection.

Diet and lifestyle recommendations for the treatment of chronic cough and chronic disease.

Chronic cough, possibly due to toxicant exposure, may be improved by using a low-risk nutrition-centred strategy. A 71-year-old man experiencing chronic cough for the past 25 years presented to the Cleveland Clinic. In recent years, the patient's cough had increased in frequency and intensity despite pulmonary interventions. The patient's social history revealed exposures as a foundry worker to dimethylethylamine and triethylamine two known respiratory irritants. The patient was placed on a nutrition programme (nutrient dense, low glycaemic index and anti-inflammatory), encouraged to use a sauna each day and placed on nutraceutical supplementation that supports liver detoxification, digestive health and inflammation reduction. Over the course of approximately 1 year, the patient experienced improvement in his cough despite the discontinuation of formal, intensive pulmonary therapy. The patient also experienced weight loss, lower blood pressure and glycaemic status improvement, as well as decreased fatigue and increased energy.

Morbidity pattern of traditional Chinese medicine primary care in the Hong Kong population.

Primary care manages >90% of illnesses requiring medical services in Hong Kong, in which 9,513 registered Chinese medicine practitioners (CMPs) provide 8.2% of the consultations. This is the first study aimed to determine the morbidity pattern in different Traditional Chinese Medicine (TCM) primary care settings in Chinese population. 55,312 patients' encounters were classified by the International Classification of Primary Care-2 (ICPC-2) from 260 of CMPs. Mean patient age was 50.5 years, with more females than males (67.0% vs 33.0%). Most patients consulted CMPs for chronic (64% vs 33.7%) rather than acute conditions. Among the 30% of patients, hypertension (49.5%) or diabetes (18.5%) were the most common co-morbidity. The most common problems presenting to CMP were respiratory (24.9%), musculoskeletal complaints (22.7%), cough (11.7%), and lower back pain (6.6%). To our knowledge, this was the first study permitting direct comparison with that presenting to Western medicine (WM) primary care by ICPC-2 systems. The results confirmed the role of CMP in primary care for musculoskeletal or chronic illnesses that they may have also received conventional WM treatment. We recommend greater effort and more resources should be invested to promote interdisciplinary communication to ensure safety and synergy of TCM and WM in primary care.

Participation in a randomised controlled feasibility study of a complex intervention for the management of the Respiratory Symptom Distress Cluster in lung cancer: patient, carer and research staff views.

This paper reports finding from a nested qualitative study designed to elicit the views and perceptions of those who participated in a randomised controlled feasibility trial testing a non-pharmacological intervention, Respiratory Distress Symptom Intervention (RDSI), for the management of the breathlessness-cough-fatigue symptom cluster in lung cancer. Semi-structured interviews were conducted with 11 lung cancer patients, three caregivers and seven researchers involved in recruitment, consent, RDSI training and delivery and participant follow-up. Thematic analysis identified key considerations including: the importance of informed consent emphasising commitment to completion of paperwork and raising awareness of potential sensitivities relating to content of questionnaires; ensuring screening for the presence of symptoms reflects the language used by patients; appreciation of the commitment required from participants to learn intervention techniques and embed them as part of everyday life; conduct of interviews with patients who decline to participate; and conduct of serial interviews with those receiving RDSI to further inform its routine implementation into clinical practice. This study will inform the development of a fully powered follow-on trial testing the hypothesis that RDSI plus usual care is superior to usual care alone in the effective management of this symptom cluster in lung cancer.

Informal Health Provider and Practical Approach to Lung Health interventions to improve the detection of chronic airways disease and tuberculosis at primary care level in Malawi: study protocol for a randomised controlled trial.

BACKGROUND: In developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at primary health care level are weak and patients turn to unskilled informal health providers to seek health care. Delayed diagnosis and treatment of these diseases facilitates increased severity and tuberculosis transmission. The World Health Organisation developed the Practical Approach to Lung Health strategy which has been shown to improve the management of both tuberculosis and chronic airways disease. The guidelines address the need for integrated guidelines for tuberculosis and chronic airways disease. Engaging with informal health providers has been shown to be effective in improving health services uptake. However, it is not known whether engaging community informal health providers would have a positive impact in the implementation of the Practical Approach to Lung Health strategy. We will use a cluster randomised controlled trial to determine the effect of using the two interventions to improve case detection and treatment of patients with tuberculosis and chronic airways disease. METHODS: A three-arm cluster randomised trial design will be used. A primary health centre catchment population will form a cluster, which will be randomly allocated to one of the arms. The first arm personnel will receive the Practical Approach to Lung Health strategy intervention. In addition to this strategy, the second arm personnel will receive training of informal health providers. The third arm is the control. The effect of interventions will be evaluated by community surveys. Data regarding the diagnosis and management of chronic cough will be gathered from primary health centres. DISCUSSION: This trial seeks to determine the effect of Informal Health Provider and Practical Approach to Lung Health interventions on the detection and management of chronic airways disease and tuberculosis at primary care level in Malawi. TRIAL REGISTRATION: The unique identification number for the registry is PACTR201411000910192--21 November 2014.

Cough reduction using capsaicin.

UNLABELLED: Chronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain. OBJECTIVES: We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing. METHODS: Twenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms. RESULTS: Three patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (p < 0.020) and in controls (p < 0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p < 0.0004) and C5 (p < 0.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (p < 0.0030) compared to the baseline scores. CONCLUSION: Capsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1).

Does respiratory muscle training improve cough flow in acute stroke? Pilot randomized controlled trial.

BACKGROUND AND PURPOSE: Cough protects the lungs from aspiration. We investigated whether respiratory muscle training may improve respiratory muscle and cough function, and potentially reduce pneumonia risk in acute stroke. METHODS: We conducted a single-blind randomized placebo-controlled trial in 82 patients with stroke (mean age, 64±14 years; 49 men) within 2 weeks of stroke onset. Participants were masked to treatment allocation and randomized to 4 weeks of daily expiratory (n=27), inspiratory (n=26), or sham training (n=25), using threshold resistance devices. Primary outcome was the change in peak expiratory cough flow of maximal voluntary cough. Intention-to-treat analyses were conducted using ANCOVA, adjusting for baseline prognostic covariates. RESULTS: There were significant improvements in the mean maximal inspiratory (14 cmH2O; P<0.0001) and expiratory (15 cmH2O; P<0.0001) mouth pressure and peak expiratory cough flow of voluntary cough (74 L/min; P=0.0002) between baseline and 28 days in all groups. Peak expiratory cough flow of capsaicin-induced reflex cough was unchanged. There were no between-group differences that could be attributed to respiratory muscle training. There were also no differences in the 90-day incidence of pneumonia between the groups (P=0.65). CONCLUSIONS: Respiratory muscle function and cough flow improve with time after acute stroke. Additional inspiratory or expiratory respiratory muscle training does not augment or expedite this improvement. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN40298220.

Integrating active tuberculosis case finding in antenatal services in Zambia.

SETTING: Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. OBJECTIVE: To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. DESIGN: Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. RESULTS: All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. CONCLUSION: There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

Adjunctive treatment with oral AKL1, a botanical nutraceutical, in chronic obstructive pulmonary disease.

PURPOSE: The objective of this pilot trial was to evaluate the safety and efficacy of AKL1, a patented botanical formulation containing extracts of Picrorhiza kurroa, Ginkgo biloba, and Zingiber officinale, as add-on therapy for patients with chronic obstructive pulmonary disease (COPD) and chronic cough. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial enrolled male and female patients >18 years old with COPD and Leicester Cough Questionnaire (LCQ) score of <18. The 10-week study period comprised a 2-week single-blind placebo run-in period followed by add-on treatment with AKL1 or placebo twice daily for 8 weeks. The primary study endpoint was the change from week 0 to week 8 in cough-related health status, as assessed by the LCQ. RESULTS: Of 33 patients enrolled, 20 were randomized to AKL1 and 13 to placebo. Patients included 19 (58%) men and 14 (42%) women of mean (standard deviation [SD]) age of 67 (9.4) years; 15 (45%) patients were smokers and 16 (49%) were ex-smokers. The mean (SD) change from baseline in LCQ score at 8 weeks was 2.3 (4.9) in the AKL1 group and 0.6 (3.7) in the placebo group, with mean difference in change of 1.8 (95% confidence interval: -1.5 to 5.1; P=0.28). The St George's Respiratory Questionnaire score improved substantially in the AKL1 treatment group by a mean (SD) of -7.7 (11.7) versus worsening in the placebo group (+1.5 [9.3]), with mean difference in change of -9.2 (95% confidence interval: -19.0 to 0.6; P=0.064). There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures, lung function, or the 6-minute walk distance. CONCLUSION: Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD.