Does hiatal hernia impact gastro-oesophageal reflux-related chronic cough?

Background: Hiatal hernia may coexist with gastro-oesophageal reflux (GOR)-related chronic cough. This study aimed to evaluate whether the presence of hiatal hernia was related to chronic cough severity and the response to antireflux therapy. Methods: This was a retrospective analysis of data on adults with GOR-related chronic cough managed in our cough centre between 2017 and 2021. Patients who had undergone chest computed tomography (CT) and in whom follow-up data were available were included. The presence and size of hiatal hernia were assessed based on thorax CT scanning. Patients were treated with modification of diet and proton pump inhibitors. The response to treatment was assessed by the change in quality of life (QOL) measured by Leicester Cough Questionnaire (LCQ) and cough severity was measured by 100-mm visual analogue scale. Results: 45 adults (28 female, 17 male) were included. Hiatal hernia was demonstrated in 12 (26.6%) patients. Patients with hiatal hernia did not differ from those without hiatal hernia in clinical characteristics, cough duration and severity and cough-related QOL. We found moderate positive correlations between maximal sagittal diameter of hiatal hernia and cough severity (ρ=0.692, p=0.013) and duration (ρ=0.720, p=0.008). Patients without hiatal hernia responded better to antireflux therapy, with significant LCQ improvement. A strong negative correlation between sagittal diameter of hiatal hernia gate and increase in LCQ (ρ= -0.764, p=0.004) was demonstrated. Conclusion: The presence of hiatal hernia identified in chest CT may impact cough severity, duration and response to antireflux treatment in patients with GOR-related chronic cough. Further prospective studies are justified to confirm significance of hiatal hernia in the management of chronic cough.

Diagnostic yield of chest radiograph in management of adults with difficult-to-treat chronic cough-retrospective study.

Background: Chest radiograph (CXR) is a routine imaging test in adults with chronic cough (CC), while value of thoracic computed tomography (CT) in these patients is still a matter of discussion. The aims of the study were to assess the diagnostic yield of CXR and to evaluate the impact of thoracic CT on management of patients with difficult-to-treat CC referred to our cough clinic. Methods: The retrospective analysis of paired CXR and CT results was performed in 189 consecutive adults treated due to CC between 2015-2019 in our cough clinic. CC was defined as cough >8 weeks being the main or isolated ailment. The sensitivity, specificity, negative/positive predictive value (NPV, PPV) and diagnostic accuracy of CXR were calculated based on chest CT scan as the "gold standard". Only those CT scans which revealed abnormalities potentially related to CC and were associated with the changes in further diagnostic or therapeutic approach were construed as relevant CT findings during final analysis. Results: The median age of patients (male/female ratio 53/136) was 58 years (IQR 44-67), only 6 subjects (3.0%) were active smokers, median CC duration was 48 months (IQR 24-120). CXR revealed abnormal findings in 23/189 (12.2%) patients. Normal CXR was confirmed by CT in 141 subjects (141/166; 84.9%). In 25/166 (15.1%) patients, CT showed abnormalities that could explain the cause of CC and changed either the diagnostic protocol or therapy. In patients with abnormal CXR, CT confirmed abnormal findings in 8 cases (8/23, 34.8%). The sensitivity, specificity, PPV, NPV, diagnostic accuracy were 24.2%, 90.4%, 34.8%, 84.9% and 78.8%, respectively. Conclusions: CXR shows a limited diagnostic yield in adults with difficult-to-treat CC referred to cough clinic. Chest CT scan may add significant data impacting the diagnostic and therapeutic approach in these patients.

Influence of Apnea Hypopnea Index and the Degree of Airflow Limitation on Endothelial Function in Patients Undergoing Diagnostic Coronary Angiography.

Background: Obstructive sleep apnea is associated with an increased prevalence of cardiovascular disease. The mechanism of these associations is not completely understood. We aimed to investigate the association of the apnea hypopnea index and the degree of airflow limitation with endothelial dysfunction. Methods: This was a single-center prospective study of patients admitted for diagnostic coronary angiography (CAG). Endothelial function was assessed by the non-invasive EndoPAT system by reactive hyperemia index (RHI) and divided into two groups: endothelial dysfunction and normal endothelial function. Sleep apnea signs were detected by WatchPAT measuring the respiratory disturbance index (pRDI), the apnea and hypopnea index (pAHI), and the oxygen desaturation index (ODI). Patients underwent spirometry and body plethysmography. Based on CAG, the severity of coronary artery disease was assessed as follows: no significant coronary artery disease, single-, two- and three-vessel disease. Results: A total of 113 patients were included in the study. Breathing disorders measured by WatchPAT and spirometry were more severe in patients with endothelial dysfunction: pRDI (27.3 vs. 14.8, p = 0.001), pAHI (24.6 vs. 10.3, p < 0.001), ODI (13.7 vs. 5.2, p = 0.002), forced expiratory volume in one second (FEV1) (81.2 vs. 89, p = 0.05). In a multivariate regression analysis, pAHI and FEV1 were independent predictors of endothelial dysfunction assessed by RHI. There was no correlation between the severity of coronary artery disease and endothelial dysfunction. Conclusions: Obstructive sleep apnea signs and greater airflow limitation were associated with endothelial dysfunction regardless of the severity of the coronary artery disease.

Inflammatory Phenotypes of Cough Variant Asthma as Response Predictors to Anti-Asthmatic Therapy.

BACKGROUND: Eosinophilic inflammatory phenotype was thought to be the most common phenotype of cough variant asthma (CVA), nevertheless other phenotypes were also reported. PURPOSE: The study aimed to analyze the inflammatory phenotypes of CVA in relation to treatment response to the stepwise anti-asthmatic treatment. PATIENTS AND METHODS: The study included 45 patients with chronic cough (CC) and suspicion of CVA (normal chest X-ray, presence of bronchial hyperresponsiveness and no history of wheezing or dyspnea) in whom induced sputum was successfully collected. Based on the cellular composition of the sputum, patients were divided into major inflammatory phenotypes: eosinophilic, neutrophilic, paucigranulocytic or mixed granulocytic. A stepwise treatment, including inhaled corticosteroids with long-acting ß2-agonist, montelukast and short-term therapy with prednisone was initiated. Good treatment response was defined as the reduction in cough severity at least 20 mm from the baseline in visual analogue scale and improvement in cough-related quality of life assessed by the Leicester cough questionnaire at least 1.3 points after any of three steps. RESULTS: Finally, 40/45 (88.9%) patients improved after therapy. Eosinophilic asthma was found in 13/40 (32.5%) patients, neutrophilic in 6/40 (15.0%) and paucigranulocytic pattern in 21/40 (52.5%) patients. No one demonstrated a mixed granulocytic phenotype. The response to the treatment was similar in all groups. However, the reduction in cough severity was inversely related to the percentage of sputum neutrophils (r = -0.44, P = 0.003). We showed that the percentage of neutrophils in sputum >46% may be considered as a predictor of poor response to anti-asthmatic therapy. CONCLUSION: The diversity of inflammatory phenotypes with paucigranulocytic preponderance was found in subjects with CVA. The response to anti-asthmatic treatment in patients with CVA was not related to the inflammatory phenotype. High neutrophil count in sputum may predict poor response to anti-asthmatic therapy in patients with CC and bronchial hyperresponsiveness.

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. The study aimed to evaluate BEC as a predictor of treatment response in all non-smoking adults with chronic cough and normal chest radiograph referred to cough clinic and in a subgroup of patients with chronic cough due to asthma or non-asthmatic eosinophilic bronchitis (NAEB). This prospective cohort study included 142 consecutive, non-smoking patients referred to our cough centre due to chronic cough. The management of chronic cough 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 and NAEB were diagnosed in 47.2% and 4.9% of patients, respectively. After 12-16 weeks of therapy, a good response to chronic cough 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). Area under the curve for all patients with chronic cough was 0.62 with the optimal BEC cut-off for prediction of treatment response set at 237 cells·µL-1 and for patients with chronic cough 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 chronic cough treated in the cough centre.

Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study.

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Chronic cough related to the upper airway cough syndrome: one entity but not always the same.

PURPOSE: Upper airway cough syndrome (UACS), described as chronic cough (CC) associated with allergic (AR), non-allergic rhinitis (NAR) or chronic rhinosinusitis (CRS), is one of the major causes of CC. We aimed to characterize a cohort of UACS patients with special attention to differences between patients with AR and NAR. METHODS: A prospective analysis of clinical data of patients, diagnosed with UACS between 2015 and 2018. RESULTS: There were 143 patients diagnosed with UACS, median age 52 years, women predominance (68.5%), The group comprised of 59 (41%) AR and 84 (59%) NAR subjects, CRS diagnosed in 17 (12%). Median cough duration: 48 months (IQR 24-120), median cough severity (VAS)-60 mm (IQR 42-78), median Leicester Cough Questionnaire (LCQ) score-11.3 (IQR 8.7-13.7), never-smokers: 70%. The most common symptoms: PND (62%), rhinorrhea (59%), nasal congestion (54%), abnormalities of sinus CT: septum deviation (62%), turbinates hypertrophy (53%), mucosal thickening (53%). UACS as the only cause of CC, was presented in 20 patients (14%). We found no differences between patients with AR and NAR in terms of age, gender, duration and severity of cough, BMI, blood eosinophil count, total IgE and FeNO. AR was associated with higher comorbidity of asthma than NAR (54% vs 35%, p = 0.019). Abnormalities in sinus CT scan were more frequently found in patients with NAR than AR (p = 0.018). CONCLUSION: NAR is the most common upper airway disease associated with UACS. Clinical characteristics of UACS patients with AR and NAR are similar with only minor differences between these groups. It seems reasonable to plan further studies concerning relationship of NAR and cough sensitivity, also in terms of potential similar neurogenic mechanism.

Expression of Inflammatory Mediators in Induced Sputum: Comparative Study in Asthma and COPD.

Asthma and COPD are the most common obstructive lung diseases characterized by inflammation in the lower airways which contribute to airflow limitation. Different inflammatory mediators are thought to play a key role in these diseases. This study was conducted in 13 patients with asthma, 12 patients with COPD, and 13 control subjects. The expression of mRNA of IL-6, IL-13, CXCL8, TSLP, IL-33, IL-25, IL-17, ECP, mast cell tryptase, CCL24, and CCL26 was assessed in induced sputum cells by real time PCR. We found that CXCL8 was strongly related to the neutrophil percentage but differed significantly in COPD and asthma patients. The expression of IL-17 was lower in patients with atopic asthma compared to non-atopic asthma. The percentage of macrophages correlated negatively with the expression of mast cell tryptase and ECP in COPD, and with CXCL8 in asthma. The expression of ECP correlated negatively with the severity of COPD symptoms measured by CAT. We conclude that asthma and COPD demonstrate a significant overlap in the airway cytokine profile. Thus, differentiation between the two diseases is difficult as based on a single cytokine, which suggests the coexistence of phenotypes sharing a common cytokine network in these obstructive lung diseases.

Menopausal asthma-much ado about nothing? An observational study.

OBJECTIVE: Menopausal asthma is considered a distinct asthma phenotype. Our aim was to identify potential specific features of asthma in postmenopausal women in a cohort of Polish females. METHODS: Asthma severity and control, pulmonary function, exhaled nitric oxide (FENO), peripheral blood and induced sputum (IS) differential cell count were compared in three groups: women with premenopausal asthma (group 1), menopausal women with pre-existing asthma (group 2A) and menopausal women with asthma onset in the perimenopausal or menopausal period (group 2B). RESULTS: We enrolled 27 women to group 1, 13 to group 2A and 16 to group 2B. Asthma severity and control, blood eosinophil count and FENO did not differ among the groups. Menopausal women had a higher incidence of irreversible airway obstruction (84.6% in group 2A and 56.2% in group 2B vs. 22.2% in group 1, p < 0.001 and p = 0.03, respectively). The proportion of patients with sputum eosinophilia was highest in menopausal women with pre-existing asthma, although the difference did not reach statistical significance (88.9% in group 2A vs. 66.7% in group 2B and 65.0% in group 1, respectively, p = 0.86). CONCLUSIONS: Menopausal women with asthma are characterized by an increased incidence of irreversible airway obstruction regardless of disease duration. This may indicate that age may contribute to pulmonary function impairment in asthmatic women independently of their hormonal status at the time of asthma diagnosis. Our results failed to confirm the presence of specific asthma features which would allow to distinguish the phenotype of menopausal asthma.

Expression of eotaxins in the material from nasal brushing in asthma, allergic rhinitis and COPD patients.

BACKGROUND: Asthma and COPD are non-infectious inflammatory diseases of the respiratory tract. Allergic rhinitis can be assumed as an intermediate condition between healthy and asthmatic state. Eotaxins are important indicators of allergic reaction. They are strong chemoattractants mainly for eosinophils but also for other cells. OBJECTIVE: We measured the level of eotaxin expression and inflammatory cell count in the material from nasal brushing in healthy controls and in patients with allergic rhinitis, asthma, and COPD. We studied the correlation between the eotaxin gene expression level in the material from nasal brushing and respiratory tests in asthma and COPD patients. METHODS: Expression of eotaxins was measured using quantitative RT-PCR. Number of eotaxin transcript copies was evaluated using real time PCR standard curve method. RESULTS: Of all eotaxins CCL24 had the highest expression in the material from nasal brushing, and its level was increased in allergic asthma. CCL11 was significantly increased in the material from nasal brushing of COPD patients. Increased levels of all three eotaxins were observed in the material from nasal brushing of patients with allergic rhinitis in season. The levels of CCL26 expression and FEV1/FVC factor were correlated negatively in the asthma group and positively in the COPD group. CONCLUSIONS: Eotaxins are crucial factors of allergic, asthmatic and also COPD inflammatory reactions. Our results suggest a dual role of CCL26 - it can act as a negative regulator for neutrophils in COPD, while in asthma it may act as a chemoatractant of eosinophils and other cells into the lung.

IL-6 and IL-13 in induced sputum of COPD and asthma patients: correlation with respiratory tests.

BACKGROUND: IL-6 is strongly implicated in the development of chronic obstructive pulmonary disease (COPD). IL-13 is the well-documented central mediator in allergic asthma. IL-6 is attributed to the proinflammatory activities in COPD as well as asthma. In COPD patients exacerbation is increased by serum IL-6. The association of IL-13 as well as IL-6 with the impaired respiratory function of asthma patients remains controversial. OBJECTIVES: The aim of this study was to compare the concentration of IL-6 and IL-13 in the induced sputum of asthma and COPD patients, and to assess the possible association of these cytokines with the impairment of lung function. METHODS: Twenty-six subjects with COPD and 18 subjects with asthma were enrolled in this study. IL-6 and IL-13 levels were measured in induced sputum by ELISA and correlated with the results of respiratory tests. RESULTS: The induced sputum of COPD patients had a significantly higher IL-6 level than the sputum of asthma subjects while no significant differences were found in the levels of IL-13. There was a statistically significant negative correlation between IL-6 level and FEV(1) or FEV(1)/FVC in asthma patients (r = -0.59 and -0.54, respectively) and a negative correlation that did not reach statistical significance between IL-6 level and FEV(1), FEV(1)% or FVC in COPD subjects (r = -0.30, -0.30 and -0.38, respectively). There was no relationship between concentrations of IL-13 and impaired respiratory function. CONCLUSIONS: Our results confirmed that IL-6, but not of IL-13, is associated with respiratory disorders in both asthma and COPD patients.