Obesity Predicts Treatment Response to Proton Pump Inhibitor Therapy in Patients with Chronic Cough.

BACKGROUND: Chronic cough management is challenging as this condition is often associated with multiple comorbidities, requiring a multidisciplinary diagnostic approach. Little is known about the characteristics of obese patients with chronic cough. This study aims to describe treatable traits of chronic cough and the response to pump proton inhibitor (PPI) therapy in this sub-group of patients. METHODS: A retrospective, observational study was performed in patients with chronic cough in a French University Hospital. Characteristics of chronic cough were analyzed for obese (N = 112) and non-obese (N = 355) patients. Refractory cough was estimated at 6 and 12 months. RESULTS: The 3 main treatable traits associated with chronic cough in obese patients and non-obese patients were gastroesophageal reflux disease (GERD), asthma, and upper airway cough syndrome (UACS). A noticeable difference was the higher frequency of GERD (47.3% vs 34.6%, p = 0.0188) and obstructive sleep apnea (OSA) (9.8% vs 3.1%, p = 0.0080) in obese patients compared to non-obese patients. Pump proton inhibitor (PPI) treatment had a significantly higher success rate in obese patients (32.5% vs 17.0%, p < 0.05) and refractory cough at 12 months was less frequently reported in obese patients (22.3% vs 34.1%, p < 0.05). CONCLUSION: In a context of chronic cough, a higher prevalence of GERD was noted in obese patients compared to non-obese patients and obese patients were more responsive to PPI treatment. Moreover, OSA was reported more frequently as a treatable trait in obese patients and should be considered early in the diagnostic evaluation. Prospective clinical studies that evaluate the contribution of obesity to chronic cough are further needed.

Impact of gender on COPD expression in a real-life cohort.

Reports regarding gender-related differences in COPD expression have provided conflicting results. In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions. For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care.

Association of chronic nasal symptoms with dyspnoea and quality-of-life impairment in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Previous studies suggested that chronic nasal symptoms (CNS) are frequent in chronic obstructive pulmonary disease (COPD) subjects, but their contribution to dyspnoea and quality-of-life (QoL) impairment is not clearly established. METHODS: Data from the French COPD cohort 'Initiatives bronchopneumopathie chronique obstructive' were analyzed to assess the frequency of CNS (rhinorrhea, obstruction, anosmia) in COPD patients and analyze their impact and associated risk factors. Univariate and multivariate analyses were performed to assess the relationship between CNS with sociodemographic and anthropometric characteristics, risk factors, respiratory symptoms, spirometry, QoL (Saint George's respiratory questionnaire (SGRQ)), dyspnoea (modified Medical Research Council (mMRC) scale), mood disorders (Hospital Anxiety and Depression Scale (HADS)), number of exacerbations and comorbid conditions. RESULTS: CNS were reported by 115 of 274 COPD subjects (42%). Among them, rhinorrhea and nasal obstruction were reported by 62% and 43%, respectively. In multivariate analysis, COPD patients with CNS had higher SGRQ total scores, corresponding to worse QoL (P = 0.01), while no independent association was found with exacerbations, lung function and HADS. Among SGRQ domains, an independent association was found with the activity score (P = 0.007). When SGRQ score was forced out of the model to avoid redundancy, mMRC score was independently associated with CNS (P = 0.01). Among risk factors, cumulative smoking, hay fever and atopic dermatitis but not occupational exposures were independently associated with CNS. CONCLUSIONS: In this group of COPD subjects, CNS were frequently observed and associated with dyspnoea and poorer QoL. CNS should be systematically assessed and could be a potential target in the management of COPD.

Novel study design to assess the utility of the copd assessment test in a primary care setting.

The quality of a consultation provided by a physician can have a profound impact on the quality of care and patient engagement in treatment decisions. When the COPD Assessment Test (CAT) was developed, one of its aims was to aid the communication between physician and patient about the impact of COPD. We developed a novel study design to assess this in a primary care consultation. Primary care physicians across five countries in Europe conducted videoed consultations with six standardised COPD patients (played by trained actors) which had patient-specific issues that the physician needed to identify through questioning. Half the physicians saw the patients with the completed CAT, and half without. Independent assessors scored the physicians on their ability to identify and address the patient-specific issues, review standard COPD aspects, their understanding of the case and their overall performance. This novel study design presented many challenges which needed to be addressed to achieve an acceptable level of robustness to assess the utility of the CAT. This paper discusses these challenges and the measures adopted to eliminate or minimise their impact on the study results.

Utility of COPD Assessment Test (CAT) in primary care consultations: a randomised controlled trial.

BACKGROUND: One of the aims of the COPD Assessment Test (CAT) is to aid communication between the physician and patient about the burden of chronic obstructive pulmonary disease (COPD) on the patient's life. AIMS: To investigate the impact of the CAT on the quality of primary care consultations in COPD patients. METHODS: Primary care physicians across Europe conducted six consultations with standardised COPD patients (played by trained actors). Physicians were randomised to see the patient with the completed CAT (CAT+ arm) or without (no CAT arm) during the consultation. These were videoed and independent assessors scored the physicians on their ability to identify and address patient-specific issues such as depression (sub-score A); review standard COPD issues such as breathlessness (sub-score B); their understanding of the case (understanding score); and their overall performance. The primary endpoint was the global score (sub-scores A+B; scale range 0-40). RESULTS: A total of 165 physicians enrolled in the study and carried out six consultations each; 882 consultations were deemed suitable for analysis. No difference was seen between the arms in the global score (no CAT arm 20.3; CAT+ arm 20.7; 95% CI -1.0 to 1.8; p=0.606) or on sub-score A (p=0.255). A statistically significant difference, though of limited clinical relevance, was observed in mean sub-score B (no CAT arm 8.8; CAT+ arm 9.6; 95% CI 0.0 to 1.6; p=0.045). There was no difference in understanding score (p=0.824) or overall performance (p=0.655). CONCLUSIONS: The CAT is a disease-specific instrument that aids physician assessment of COPD. It does not appear to improve detection of non-COPD symptoms and co-morbidities.

Association between occupational exposure and the clinical characteristics of COPD.

BACKGROUND: The contribution of occupational exposures to COPD and their interaction with cigarette smoking on clinical pattern of COPD remain underappreciated. The aim of this study was to explore the contribution of occupational exposures on clinical pattern of COPD. METHODS: Cross-sectional data from a multicenter tertiary care cohort of 591 smokers or ex-smokers with COPD (median FEV1 49%) were analyzed. Self-reported exposure to vapor, dust, gas or fumes (VDGF) at any time during the entire career was recorded. RESULTS: VDGF exposure was reported in 209 (35%) subjects aged 31 to 88 years. Several features were significantly associated with VDGF exposure: age (median 68 versus 64 years, p < 0.001), male gender (90% vs 76%; p < 0.0001), reported work-related respiratory disability (86% vs 7%, p < 0.001), current wheezing (71% vs 61%, p = 0.03) and hay fever (15.5% vs 8.5%, p < 0.01). In contrast, current and cumulative smoking was less (p = 0.01) despite similar severity of airflow obstruction. CONCLUSION: In this patient series of COPD patients, subjects exposed to VDGF were older male patients who reported more work-related respiratory disability, more asthma-like symptoms and atopy, suggesting that, even in smokers or ex-smokers with COPD, occupational exposures are associated with distinct patients characteristics.

Alveolar and blood T lymphocyte profiles in Pneumocystis jirovecii-positive patients: effects of HIV status.

BACKGROUND: There are substantial differences in the risk evaluation, clinical presentation, and outcome of Pneumocystis pneumonia between human immunodeficiency virus (HIV)-positive and HIV-negative immunocompromised patients. To compare the host immune defenses against Pneumocystis jirovecii, the blood and alveolar lymphocyte profile was explored in these 2 populations. METHODS: The total, CD3(+), CD4(+), and CD8(+) T-lymphocyte counts were measured in the blood and alveoli of immunocompromised patients with a P. jirovecii DNA detected in their bronchoalveolar lavage samples, according to their HIV status. RESULTS: In blood and alveoli, the CD4(+) and CD8(+) T-lymphocyte counts were higher and lower, respectively, in the HIV-negative group. The threshold for initiating prophylaxis in HIV-positive persons, 200 CD4(+) T cells/µL, was not pertinent for HIV-negative patients. The P. jirovecii burden correlated with the blood CD4(+) T-cell counts in the HIV-positive but not in the HIV-negative group. Nevertheless, whatever the HIV status, a correlation was observed between alveolar CD4(+) T cells and the P. jirovecii burden. CONCLUSIONS: The T-lymphocyte profile was different between HIV-positive and HIV-negative patients with P. jirovecii, suggesting a distinct pathogenesis. Alveolar CD4(+) T cells could be critical to explain the development of Pneumocystis pneumonia but may also be important for evaluation of disease risk, mostly among HIV-negative immunocompromised patients.

Impact of chest computed tomography scan on the management of patients with chronic cough.

A quarter of chronic cough (CC) patients have an abnormal chest CT scan but the effect of this on CC management is limited. Chest CT scan should not be routinely performed in CC, particularly in patients with dry cough. https://bit.ly/3Bl3EeE.

Vaccination for Respiratory Infections in Patients with Heart Failure.

Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.

Predictors in routine practice of 6-min walking distance and oxygen desaturation in patients with COPD: impact of comorbidities.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m2), low BMI (BMI <18.5 kg/m2), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r2=0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r2=0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters.

Idiopathic hemoptysis in pregnant women: a distinct entity?

In pregnant women, the reported cases of hemoptysis were most often mild and had an identified cause. Between November 2003 and January 2006, three pregnant women at 16-20 weeks gestation were admitted to our respiratory intensive care unit for massive hemoptysis. One of the women had experienced mild hemoptysis, considered as idiopathic, during her first pregnancy, with no recurrence until her second pregnancy. In all three cases, hemoptysis was massive. CT scan after iodine injection did not reveal any cause. Opacification of the bronchial artery showed hyperemia from abnormally dilated and tortuous bronchial arteries. Bronchial artery embolization (BAE) was performed in all three patients, successfully in two. Intravenous vasopressin was used as second-line treatment for recurrent bleeding after BAE in one patient. The women carried the pregnancy to term with delivery of healthy infants. Further complete investigation after the births did not identify any possible local (pulmonary) or general cause of bleeding in these three patients. Although these cases could be considered idiopathic, the close association with duration of pregnancy suggests the hemoptysis may be related to hormonal changes.

Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD.

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan-Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

Impact of current cough on health-related quality of life in patients with COPD.

BACKGROUND: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD. METHODS: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities. RESULTS: One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]). In univariate analyses, health-related quality of life (Saint George's respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54). CONCLUSION: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.

Improvement after lung volume reduction surgery: a role for inspiratory muscle adaptation.

In severe emphysema, lung volume reduction surgery (LVRS) can improve lung function and exercise tolerance. The maximal changes of forced expiratory volume in 1s (FEV(1)) and lung volume occur early after surgery, whereas maximal improvement of exercise tolerance occurs later. We tested the hypothesis that secondary adaptation of inspiratory muscles could explain this delayed clinical improvement. In that purpose, we evaluated nine consecutive patients before LVRS and up to 9 months post-operatively. Six weeks after LVRS, we observed an increase in FEV(1) and 6 min walk distance (6MWD). The gain in sniff nasal inspiratory pressure (SNIP) was inversely proportional to lung volume loss. Values of FEV(1) and lung volume were maintained throughout follow-up whereas SNIP values significantly increased from 6 weeks to 6 months post-LVRS. In the meantime, we observed an increase in 6MWD correlated with the SNIP increase. This suggests that in patients undergoing LVRS, early improvement of SNIP is proportional to decrease in lung volume whereas the further delayed improvement may be due, at least in part, to adaptation of the inspiratory muscles.

Differential effects of low and high-dose estradiol on airway reactivity in ovariectomized rats.

The aim of this animal study was to test the hypothesis that low and high doses of 17beta-estradiol (E2) may differentially influence airway responsiveness. Ovariectomized female rats received either placebo or E2 (10 or 100 microg/kg per day) for 21 days. The concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC200 RL) was calculated as the in vivo index of airway responsiveness. Ex vivo airway responsiveness was evaluated by the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Rats treated with low-dose E2 were less responsive to ACh than rats given either placebo or high-dose E2 (P=0.003). Ex vivo, low-dose E2 treatment decreased (P=0.01) and high-dose E2 increased the potency of ACh (P<0.001) compared to placebo. E2 treatment did not alter smooth muscle cross-sectional area or epithelium thickness. Accumulation of liquid within the tracheal mucosa was moderately enhanced by high-dose E2 treatment compared with animals given either placebo or low-dose E2 (P=0.03). We conclude that E2 treatment has differential, dose-dependent effects on airway responsiveness to acetylcholine.

[COPD: beyond the respiratory system]. / La BPCO au-delà de l'appareil respiratoire.

COPD is a respiratory disease associated with multiple extrapulmonary comorbidities: cardiovascular diseases, osteoporosis, depression and psychological disorders are the most prevalent. Comorbidities, especially ischemic heart disease, represent a major cause of morbidity and mortality in COPD patients. The putative link between COPD and comorbidities could be the low-grade systemic inflammation, which is common in COPD. The presence of multiple comorbidities has a strong impact on the management of COPD patients.