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.

European Respiratory Society guidelines on the diagnosis and treatment of chronic cough in adults and children

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice

The detailed pathogenesis of eosinophilic bronchitis (EB) remains unclear. Transglutaminase 2 (TG2) has been implicated in many respiratory diseases including asthma. Herein, we aim to assess preliminarily the relationship of TG2 with EB in the context of the development of an appropriate EB model through ovalbumin (OVA) sensitization and challenge in the C57BL/6 mouse strain. Our data lead us to propose a 50 μg dose of OVA challenge as appropriate to establish an EB model in C57BL/6 mice, whereas a challenge with a 400 μg dose of OVA significantly induced asthma. Compared to controls, TG2 is up-regulated in the airway epithelium of EB mice and EB patients. When TG2 activity was inhibited by cystamine treatment, there were no effects on airway responsiveness; in contrast, the lung pathology score and eosinophil counts in bronchoalveolar lavage fluid were significantly increased whereas the cough frequency was significantly decreased. The expression levels of interleukin (IL)-4, IL-13, IL-6, mast cell protease7 and the transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) were significantly decreased. These data open the possibility of an involvement of TG2 in mediating the increased cough frequency in EB through the regulation of TRPA1 and TRPV1 expression. The establishment of an EB model in C57BL/6 mice opens the way for a genetic investigation of the involvement of TG2 and other molecules in this disease using KO mice, which are often generated in the C57BL/6 genetic background.

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.