Blood eosinophils as a predictor of treatment response in adults with difficult-to-treat chronic cough

There is lack of evidence on the role of blood eosinophil count (BEC) as a predictor of treatment response in patients with chronic cough (CC). The study aimed to evaluate BEC as a predictor of treatment response in all non-smoking adults with CC and normal chest X-ray referred to cough clinic and in subgroup of patients with CC due to asthma or NAEB (non-asthmatic eosinophilic bronchitis).This prospective cohort study included 142 consecutive, non-smoking patients referred to our cough centre due to CC. The management of CC was performed according to the current recommendations. At least a 30 mm decrease of 100-mm visual analogue scale in cough severity and a 1.3 points improvement in Leicester Cough Questionnaire were classified as a good therapeutic response.There was a predominance of females (72.5%), median age 57.5 years with long-lasting, severe cough (median cough duration 60 months, severity 55/100 mm). Asthma, NAEB were diagnosed in 47.2% and 4.9% of patients, respectively. After 12–16 weeks of therapy, a good response to CC treatment was found in 31.0% of all patients. A weak positive correlation was demonstrated between reduction in cough severity and BEC (r=0.28, p<0.001). AUC for all patients with CC was 0.62 with the optimal BEC cut-off for prediction of treatment response set at 237 cells·µL−1 and for patients with CC due to asthma/NAEB was 0.68 (95% CI 0.55–0.81) with the cut-off at 150 cells·µL−1.BEC is a poor predictor of treatment response in adults with CC treated in the cough centre.

Application of Nightingale's Environmental Theory: The Effect of Heliotherapy on The Clinical Improvements in Individuals with Tuberculosis

Tuberculosis is a global health problem. Sunlight can trigger vitamin Dproduction, so it increases the immunity system. This study analysesNightingale's environmental theory through the effect of heliotherapy on theclinical improvements in individuals with tuberculosis. It was a quantitativestudy using a quasi-experimental design with a pretest-posttest approach and acontrol group. In addition, the population was 59 individuals with tuberculosisin Depok Sleman District, Yogyakarta. Meanwhile, there were 24 respondentsby purposive sampling method. The intervention group at Depok 3 Public Health Centre (PHC) was 17 respondents with heliotherapy and anti-tuberculosis drugs, while the control group at Depok 2 PHC was 17 respondents with anti-tuberculosis drugs. The independent variable washeliotherapy, while the dependent variable was the clinical improvementsconsisting of weight, cough, and shortness of breath. Heliotherapy wasconducted for four weeks with an intensity of four times a week for 25minutes a day. Instruments used weigh scale, Borg Scale, and Leicester cough questionnaire. In addition, data analysis used the Wilcoxon Test and paired T-Test with a significance of 0.05. The results showed that there were clinical improvements in the intervention group (p=0.000). In addition, there wereincreased clinical improvements in weight and cough scores in the controlgroup (p=0.000). However, there was no significant difference in the shortnessof breath score in the control group (p=0.06). In conclusion, the application ofNightingale's environmental theory through heliotherapy affects clinicalimprovements in individuals with tuberculosis.

Association between chronic idiopathic cough and sensitive skin syndromes is a new argument in favor of common neuropathic pathways: results from a survey on 4050 subjects

Sensitive skin syndrome has a neuropathic origin, which is why it is frequently associated with irritable bowel syndrome. We have looked for a possible association with chronic cough, which is commonly maintained by neurogenic mechanisms, whatever the initial cause(s). A survey was carried out on a representative sample of the population over 15 years of age using the quota method. The questionnaire included sociodemographic data and questions about sensitive skin, the presence of chronic cough, smoking and possible causes of chronic cough. Chronic cough was assessed by the Leicester Cough Questionnaire, and 4050 subjects responded (mean age: 45 years). Overall, 12.2% of subjects with a chronic cough were compared to the 87.8% without any cough. Among them, 72.5% had sensitive skin (vs. 47.8%, p < 0.001); additionally, 17.4% of the subjects with sensitive skin had a chronic cough (vs. 6.9% if no sensitive skin). These proportions were higher if very sensitive skin was reported. The risk of having chronic cough was twice as high if sensitive skin was reported [OR = 1.9 (1.5–2.4), p < 0.001]. The risk of having sensitive skin was also twice as high for chronic cough. Thus, chronic cough and sensitive skin are frequently associated. This association represents a new argument in favor of a neuropathic nature of sensitive skin. Sensitive skin and chronic cough are both modes of overreaction to environmental factors, which tend to be autonomized by neurogenic mechanisms. Dermatologists should ask their patients if they have a chronic cough, and pneumologists should ask about the presence of sensitive skin.

Flupentixol/melitracen for chronic refractory cough after treatment failure with other neuromodulators

BACKGROUND: Gabapentin and baclofen are recommended for the treatment of chronic refractory cough (CRC). We investigated the efficacy of flupentixol/melitracen in patients unresponsive to these neuromodulators.METHODS: A total of 101 patients with CRC who failed to respond to gabapentin and baclofen were recruited, and treated with flupentixol/melitracen. The prevalence of cough resolution and changes in the Cough Symptom Score (CSS), cough thresholds to capsaicin, Hull Airway Reflux Questionnaire (HARQ), Leicester Cough Questionnaire (LCQ), Generalized Anxiety Disorder-7, Hamilton Anxiety Rating Scale, Patient Health Questionnaire-9, and Hamilton Depression Rating Scale-24 were evaluated after treatment.RESULTS: Ninety-eight patients (97.0%) completed the study. The overall successful cough resolution rate was 62.4% (63/101). Cough resolution was accompanied by an obvious decrease in the CSS and HARQ score and a remarkable increase in cough thresholds to capsaicin challenge and LCQ score, whereas anxiety and depression scores did not change significantly. The prevalence of adverse effects (e.g., insomnia and dizziness) was 21.8%. The prevalence of cough recurrence within 2 weeks after treatment cessation was 17.8%.CONCLUSION: Flupentixol/melitracen may be an efficacious option for CRC unresponsive to other neuromodulators.

Co-trimoxazole to reduce mortality, transplant, or unplanned hospitalisation in people with moderate to very severe idiopathic pulmonary fibrosis: the EME-TIPAC RCT

Background Idiopathic pulmonary fibrosis is an irreversible fibrosing lung disorder with a poor prognosis. Current treatments slow the rate of decline in lung function and may influence survival, but they have a significant side-effect profile and so additional therapeutic options are required. People with idiopathic pulmonary fibrosis have altered innate immunity and altered lung microbiota, with the bacterial burden relating to mortality. Two randomised controlled trials have demonstrated beneficial effects with co-trimoxazole (SEPTRIN®; Essential Generics Ltd, Egham, UK; Chemidex Generics Ltd, Egham, UK), with the suggestion of an improvement in rates of survival. Objectives To determine the clinical efficacy of co-trimoxazole in people with moderate to severe idiopathic pulmonary fibrosis. Design A Phase II, double-blind, placebo-controlled, parallel-group, randomised multicentre study. Setting UK specialist interstitial lung disease centres. Participants Patients who were randomised had idiopathic pulmonary fibrosis diagnosed by a multidisciplinary team. In addition, patients had significant breathlessness (i.e. a Medical Research Council Dyspnoea Scale score of > 1) and impaired lung function (i.e. a forced vital capacity of < 75% predicted). Patients could be taking licensed medication for idiopathic pulmonary fibrosis, but were excluded if they had significant comorbidities, including airflow obstruction. Intervention Oral co-trimoxazole, 960 mg twice per day (two 480-mg tablets twice per day), compared with placebo tablets (two tablets twice per day) for a median of 27 months (range 12–42 months). Otherwise, both trial groups had standard care. Main outcome measures The primary outcome was the time to death (all causes), transplant or first non-elective hospital admission. Secondary outcomes were the individual components of the primary end point and the number of respiratory-related events. Questionnaires (the King’s Brief Interstitial Lung Disease questionnaire; the Medical Research Council Dyspnoea Scale; EuroQol-5 Dimensions, five-level version; the Leicester Cough Questionnaire; and the Cough Symptom Score) and lung function tests (forced vital capacity and diffusing capacity for carbon monoxide) were undertaken at baseline and at 12 months. Results The trial randomised a total of 342 (295 male) patients (active treatment group, n = 170; placebo group, n = 172), using minimisation for hospital and receipt of licensed antifibrotic medication, from 39 UK hospitals. The patients had a mean (standard deviation) age of 71.3 years (7.47 years) and a mean forced vital capacity of 2.25 l (0.56 l). A total of 137 (40%) patients were taking pirfenidone (Esbriet, Roche Holding AG, Basel, Switzerland) and 116 (34%) were taking nintedanib (Ofev®, Boehringer Ingelheim, Brackness, UK). There was one post-randomisation exclusion from the co-trimoxazole group, but no withdrawals. There was no difference in the time to event for the composite primary end point (co-trimoxazole: hazard ratio 1.2, 95% confidence interval 0.9 to 1.6; p = 0.319). Likewise, there was no difference in other event outcomes, lung function measurements or patient-reported outcomes, other than a beneficial effect on the total Leicester Cough Questionnaire score, the social domain of the Leicester Cough Questionnaire score and the chest domain of the King’s Brief Interstitial Lung Disease questionnaire in the adjusted analysis. The repeated-measures analysis showed a significant overall difference in Cough Symptom Score. There were significantly more reports of nausea, but fewer reports of diarrhoea, with co-trimoxazole; however, differences in frequency of hyperkalaemia, rash and headache were not significant. The limitations of the trial were that it was not possible to evaluate the lung microbiota, there were missing data for secondary end points and there was no health economic analysis. Conclusion These results suggest that co-trimoxazole does not reduce the likelihood of death or number of hospitalisations among people with idiopathic pulmonary fibrosis with moderate to severe idiopathic pulmonary fibrosis. Further work is required to evaluate the effect in subgroups of individuals with idiopathic pulmonary fibrosis or the effect of antibiotics with different antibacterial properties. Trial registration Current Controlled Trials ISRCTN17464641. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 9. See the NIHR Journals Library for further project information.

Differential features of chronic cough according to etiology and the simple decision tree for predicting causes

Finding etiology of chronic cough is an essential part of treatment. Although guidelines include many laboratory tests for diagnosis, these are not possible in many primary care centers. We aimed to identify the characteristics and the differences associated with its cause to develop a clinical prediction model. Adult subjects with chronic cough who completed both Korean version of the Leicester Cough Questionnaire (K-LCQ) and COugh Assessment Test (COAT) were enrolled. Clinical characteristics of each etiology were compared using features included in questionnaires. Decision tree models were built to classify the causes. A total of 246 subjects were included for analysis. Subjects with asthma including cough variant asthma (CVA) suffered from more severe cough in physical and psychological domains. Subjects with eosinophilic bronchitis (EB) presented less severe cough in physical domain. Those with gastro-esophageal reflux disease (GERD) displayed less severe cough in all 3 domains. In logistic regression, voice hoarseness was an independent feature of upper airway cough syndrome (UACS), whereas female sex, tiredness, and hypersensitivity to irritants were predictors of asthma/CVA; less hoarseness was a significant feature of EB, and feeling fed-up and hoarseness were less common characteristics of GERD. The decision tree was built to classify the causes and the accuracy was relatively high for both K-LCQ and COAT, except for UACS. Voice hoarseness, degree of tiredness, hypersensitivity to irritants and feeling fed-up are important features in determining the etiologies. The decision tree may further assists classifying the causes of chronic cough.

Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant

Purpose This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. Methods Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics. Results Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). Conclusion Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. Trial registration: ClinicalTrials.gov, NCT02612610; registered November 20, 2015