ABSTRACT
Background: The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ). Methods: The kinetics of PETCO2 during the HPTest were mathematically modeled and compared between 37 HVS patients (NQ ≥23/64) and 37 healthy controls (NQ <23/64) matched for gender, age, and body dimensions. AUC values with sensitivity and specificity were calculated, and analysis was monitored in a validation cohort of 152 routine HPTests. Results: A threshold value of a less than 12.8 mmHg increment of PETCO2 at the 5th minute of the recovery phase of the HPTest diagnosed HVS patients with excellent sensitivity (0.92) and specificity (0.84). These results were confirmed in the validation cohort, highlighting the presence of 24% false positives/negatives when diagnosing on the basis of complaints in the NQ. Conclusions: For HVS diagnosis, we suggest considering the HPTest, which can more reliably reflect the mechanisms of CO2 homeostasis and the response of the respiratory center to a stimulus, regardless of the subjective onset of symptoms.
ABSTRACT
Eosinophils are rare, multifunctional granulocytes. Their growth, survival, and tissue migration mainly depend on interleukin (IL)-5 in physiological conditions and on IL-5 and IL-33 in inflammatory conditions. Preclinical evidence supports an immunological role for eosinophils as innate immune cells and as agents of the adaptive immune response. In addition to these data, several reports show a link between the outcomes of patients treated with immune checkpoint inhibitors (ICI) for advanced cancers and blood eosinophilia. In this review, we present, in the context of non-small cell lung cancer (NSCLC), the biological properties of eosinophils and their roles in homeostatic and pathological conditions, with a focus on their pro- and anti-tumorigenic effects. We examine the possible explanations for blood eosinophilia during NSCLC treatment with ICI. In particular, we discuss the value of eosinophils as a potential prognostic and predictive biomarker, highlighting the need for stronger clinical data. Finally, we conclude with perspectives on clinical and translational research topics on this subject.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Biomarkers , Carcinoma, Non-Small-Cell Lung/pathology , Eosinophils/pathology , Humans , Immune Checkpoint Inhibitors , Immunotherapy , Lung Neoplasms/pathologyABSTRACT
BACKGROUND: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. METHODS: TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. RESULTS: Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. CONCLUSION: TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.
Subject(s)
Denervation/methods , Forced Expiratory Volume/physiology , Lung/innervation , Pulmonary Disease, Chronic Obstructive/surgery , Quality of Life , Bronchoscopy , Double-Blind Method , Female , Follow-Up Studies , Humans , Lung/diagnostic imaging , Male , Prospective Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Time FactorsABSTRACT
OBJECTIVE: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients. DATA SOURCES: PubMed. STUDY SELECTION: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected. RESULTS: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes. CONCLUSION: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenergic beta-2 Receptor Agonists/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Delayed-Action Preparations , Humans , Referral and Consultation , Severity of Illness IndexSubject(s)
Airway Obstruction/therapy , Bronchoscopy/methods , COVID-19/therapy , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment , Aged , Airway Obstruction/etiology , Bronchoalveolar Lavage , Bronchoscopes , COVID-19/complications , COVID-19/prevention & control , COVID-19/transmission , Critical Care , Disposable Equipment , Female , Humans , Intensive Care Units , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/microbiology , Male , Middle Aged , Pandemics , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pulmonary Medicine , SARS-CoV-2ABSTRACT
BACKGROUND: Immunotherapy represents a recent milestone in the treatment of lung cancer, particularly with the rapidly expanding development of monoclonal antibodies targeting checkpoint inhibitors in the programmed cell death-1 (PD-1) pathway, such as nivolumab and pembrolizumab. Classical auto-immune side effects of these treatments, often called immune-related adverse events (irAEs), can affect multiple organs, including the lungs in which potentially life-threatening pneumonitis may require rapid treatment with high doses of corticosteroids. Nevertheless, the occurrence of severe infections in cancer patients treated with nivolumab, outside the context of immunosuppressive therapy, is a complication that has rarely been reported in the literature. CLINICAL CASES: We report two cases of severe pulmonary infection with unusual microbes, Mycobacterium tuberculosis and Aspergillus fumigatus, in patients treated with nivolumab for non-small cell lung cancer. CONCLUSION: Ruling out pulmonary infections may require extensive investigation, as these may have an atypical presentation due to immunomodulation. Furthermore, treating the patient with corticosteroids for immune-related pneumonia could lead to a fatal outcome in this context. This report highlights the importance of excluding the presence of opportunistic infections and tuberculosis before considering immune-related pulmonary toxicity with or without a history of prior corticosteroid use. These cases also emphasize the potential value of tuberculosis screening in patients treated with PD-1 checkpoint inhibitors.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Invasive Pulmonary Aspergillosis/diagnosis , Lung Neoplasms/drug therapy , Nivolumab/adverse effects , Tuberculosis, Pulmonary/diagnosis , Aged , Antifungal Agents/therapeutic use , Antitubercular Agents/therapeutic use , Female , Humans , Immunocompromised Host , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/immunology , Male , Middle Aged , Severity of Illness Index , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/immunologyABSTRACT
BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. OBJECTIVES: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions. METHODS: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time. RESULTS: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/µL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. CONCLUSIONS: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy. TRIAL REGISTRATION: ClinicalTrials.gov number. NCT02135354 .
Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Disease Progression , Patient Readmission/trends , Pulmonary Disease, Chronic Obstructive/drug therapy , Severity of Illness Index , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Treatment FailureABSTRACT
RATIONALE: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. OBJECTIVES: To assess safety, feasibility, and dosing of TLD in patients with moderate to severe COPD using a novel device design. METHODS: Thirty patients with COPD (forced expiratory volume in 1 s 30-60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. RESULTS: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. CONCLUSIONS: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.
Subject(s)
Bronchoscopy/methods , Lung/innervation , Parasympathectomy/methods , Pulmonary Disease, Chronic Obstructive/surgery , Aged , Female , Humans , Male , Middle AgedABSTRACT
Early detection and treatment are critical for improving the outcome of patients with cancer1. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma2,3. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients. We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to cancerous tissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial-mesenchymal transition in the invasive stage of cancer. We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy-based chemopreventive approaches for individuals who are at high risk of developing lung cancer.
Subject(s)
Carcinogenesis/immunology , Carcinogenesis/pathology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Tumor Escape/immunology , Adult , Aged , Carcinogenesis/drug effects , Carcinogenesis/genetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Early Detection of Cancer , Epithelial-Mesenchymal Transition , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Middle Aged , Neoplasm Invasiveness , Tumor Escape/drug effects , Tumor Escape/genetics , Tumor MicroenvironmentABSTRACT
Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined.Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care.Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated the TF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or all-cause mortality.Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P = 0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal.Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Treatment Failure , Administration, Inhalation , Adrenergic beta-Agonists/therapeutic use , Aged , Clindamycin/therapeutic use , Disease Progression , Double-Blind Method , Drug Therapy, Combination , Female , Forced Expiratory Volume , Glucocorticoids/therapeutic use , Hospitalization , Humans , Macrolides/therapeutic use , Male , Middle Aged , Mortality , Muscarinic Antagonists/therapeutic use , Patient Readmission , Pulmonary Disease, Chronic Obstructive/physiopathology , Quinolones/therapeutic use , Vital Capacity , beta-Lactams/therapeutic useABSTRACT
The interpretation of pulmonary function tests (PFTs) to diagnose respiratory diseases is built on expert opinion that relies on the recognition of patterns and the clinical context for detection of specific diseases. In this study, we aimed to explore the accuracy and interrater variability of pulmonologists when interpreting PFTs compared with artificial intelligence (AI)-based software that was developed and validated in more than 1500 historical patient cases.120 pulmonologists from 16 European hospitals evaluated 50 cases with PFT and clinical information, resulting in 6000 independent interpretations. The AI software examined the same data. American Thoracic Society/European Respiratory Society guidelines were used as the gold standard for PFT pattern interpretation. The gold standard for diagnosis was derived from clinical history, PFT and all additional tests.The pattern recognition of PFTs by pulmonologists (senior 73%, junior 27%) matched the guidelines in 74.4±5.9% of the cases (range 56-88%). The interrater variability of κ=0.67 pointed to a common agreement. Pulmonologists made correct diagnoses in 44.6±8.7% of the cases (range 24-62%) with a large interrater variability (κ=0.35). The AI-based software perfectly matched the PFT pattern interpretations (100%) and assigned a correct diagnosis in 82% of all cases (p<0.0001 for both measures).The interpretation of PFTs by pulmonologists leads to marked variations and errors. AI-based software provides more accurate interpretations and may serve as a powerful decision support tool to improve clinical practice.
Subject(s)
Artificial Intelligence , Pulmonary Medicine , Respiratory Function Tests , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , SoftwareABSTRACT
Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD. While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with - according to Belgian market research data - up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting ß2-adrenoreceptor agonist. Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD. However, historical habits appear difficult to change even in the light of recent scientific evidence. We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Bronchodilator Agents/administration & dosage , Inappropriate Prescribing/prevention & control , Prescription Drug Overuse/prevention & control , Pulmonary Disease, Chronic Obstructive/drug therapy , Withholding Treatment , Administration, Inhalation , Asthma/complications , Asthma/drug therapy , Drug Therapy, Combination , Humans , Pulmonary Disease, Chronic Obstructive/complicationsABSTRACT
RATIONALE AND OBJECTIVES: Computed tomography (CT) airways measurements can be used as surrogates to spirometric measurements for assessing bronchodilation in a particular patient with chronic obstructive pulmonary disease. Although spirometric measurements show variations within the opening hours of a hospital department, we aimed to compare the variability of CT airways measurements between morning and afternoon in patients with chronic obstructive pulmonary disease to that of spirometric measurements. MATERIALS AND METHODS: Twenty patients had pulmonary function tests and CT around 8 am and 4 pm. Luminal area (LA) and wall thickness (WT) of third and fourth generation airways were measured twice by three readers. The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (âWAPi10) were calculated. The effects of examination time, reader, and measurement session on CT airways measurements were assessed, and the variability of these measurements was compared to that of spirometric measurements. RESULTS: Variability of LA3rd and LA4th was greater than that of spirometric measurements (P values ranging from <.001 to .033). There was no examination time effect on âWAPi10, WT3rd, LA4th, or WA%4th (P values ranging from .102 to .712). There was a reader effect on all CT airways measurements (P values ranging from <.001 to .028), except in WT3rd (P> .999). There was no effect of measurement session on any CT airway measurement (P values ranging from .535 to >.999). CONCLUSION: As the variability of LA3rd and LA4th is greater than that of spirometric measurements, clinical studies should include cohorts with larger numbers of patients when considering LA than when considering spirometric measurements as end points.
Subject(s)
Bronchi/diagnostic imaging , Bronchi/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/physiopathology , Tomography, X-Ray Computed , Aged , Female , Humans , Male , Middle Aged , Spirometry , Time FactorsABSTRACT
BACKGROUND AND OBJECTIVE: Malignant pleurisy is associated with advanced oncological disease and dyspnoea is the most common presenting symptom. Pleurodesis is the preferred palliative and supportive treatment option, targeting symptom relief. The identification of clinical and endoscopic features that determine the success of talc pleurodesis in malignant pleurisy could guide clinical decision-making. METHODS: All symptomatic patients with malignant pleurisy subjected to talc pleurodesis through medical thoracoscopy between January 2012 and December 2015 were included. Univariate and multivariate analyses were performed to identify factors associated with successful pleurodesis. RESULTS: Of the 155 patients, 122 (78%) were classified as having a successful pleurodesis based on clinical and radiological criteria. Factors associated with unsuccessful pleurodesis (univariate analysis) were the presence of pleural adhesions (odds ratio (OR): 0.43 (95% CI: 0.19-0.96); P = 0.04), extensive spread of pleural lesions (OR: 0.17 (95% CI: 0.05-0.59); P = 0.001), the use of systemic corticosteroids (OR: 0.28 (95% CI: 0.10-0.83); P = 0.02) and a prolonged time period between the clinical diagnosis of the pleural effusion and the moment of pleurodesis (OR: 0.14 (95% CI: 0.06-0.32); P < 0.0001). The latter being associated with failure of pleurodesis in a multivariate analysis (OR: 0.08 (95% CI: 0.01-0.25); P < 0.0001). Chest ultrasound prior to pleurodesis showed a sensitivity of 91% and a specificity of 88% in predicting the success of pleurodesis. CONCLUSION: The success rate of pleurodesis in malignant pleurisy could potentially be enhanced by correct patient selection and early referral for pleurodesis. Ultrasonic assessment of pleural adhesions and potential lung expansion prior to pleurodesis is useful in clinical decision-making.
Subject(s)
Pleural Effusion, Malignant/therapy , Pleurodesis/methods , Talc/therapeutic use , Thoracoscopy/methods , Adrenal Cortex Hormones/therapeutic use , Aged , Breast Neoplasms/complications , Carcinoma/complications , Digestive System Neoplasms/complications , Female , Humans , Lung Neoplasms/complications , Male , Mesothelioma/complications , Middle Aged , Multivariate Analysis , Odds Ratio , Ovarian Neoplasms/complications , Pleural Diseases/diagnostic imaging , Pleural Diseases/epidemiology , Pleural Effusion, Malignant/diagnostic imaging , Pleural Effusion, Malignant/epidemiology , Pleural Effusion, Malignant/etiology , Pleural Neoplasms/complications , Pleurisy/diagnostic imaging , Pleurisy/epidemiology , Pleurisy/etiology , Pleurisy/therapy , Retrospective Studies , Tissue Adhesions/epidemiology , Treatment Failure , Treatment Outcome , UltrasonographyABSTRACT
BACKGROUND: Dual bronchodilation combining a long-acting ß2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 µg and LAMA, glycopyrronium 50 µg (IND/GLY 110/50 µg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. METHODS: The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 µg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. RESULTS: The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. CONCLUSIONS: IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01985334 .
Subject(s)
Adrenergic beta-2 Receptor Agonists/administration & dosage , Bronchodilator Agents/administration & dosage , Drug Substitution , Glycopyrrolate/administration & dosage , Indans/administration & dosage , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Adult , Aged , Bronchodilator Agents/adverse effects , Disease Progression , Drug Combinations , Dyspnea/diagnosis , Dyspnea/drug therapy , Dyspnea/physiopathology , Europe , Female , Forced Expiratory Volume , Glycopyrrolate/adverse effects , Health Status , Humans , Indans/adverse effects , Lung/physiopathology , Male , Middle Aged , Muscarinic Antagonists/adverse effects , Patient Safety , Prospective Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Quinolones/adverse effects , Recovery of Function , Risk Factors , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. METHODS: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. RESULTS: To diagnose ACOS in COPD patients, major criteria were "high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second ≥400 mL)" and "high degree of response to bronchodilators (>200 mL and ≥12% predicted above baseline)". Minor criteria were "personal/family history of atopy and/or IgE sensitivity to ≥1 airborne allergen", "elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide", "diagnosis of asthma <40 years of age"; "symptom variability", and "age (in favor of asthma)". To diagnose ACOS in asthma patients, major criteria were "persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)" and "exposure to noxious particles/gases, with ≥10 pack-years for (ex-)smokers"; minor criteria were "lack of response on acute bronchodilator test"; "reduced diffusion capacity"; "limited variability in airway obstruction"; "age >40 years"; "emphysema on chest computed tomography scan". CONCLUSION: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD.
Subject(s)
Asthma/diagnosis , Decision Support Techniques , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonologists , Respiratory Function Tests , Surveys and Questionnaires , Administration, Inhalation , Asthma/drug therapy , Asthma/epidemiology , Asthma/physiopathology , Belgium/epidemiology , Bronchodilator Agents/administration & dosage , Consensus , Female , Forced Expiratory Volume , Health Surveys , Humans , Lung/drug effects , Male , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Syndrome , Vital CapacityABSTRACT
BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first-choice options per GOLD category without specification. OBJECTIVES: To evaluate the level of medical experts' consensus on their preferred first-choice treatment within different COPD categories. METHODS: A two-round Delphi Panel consisting of 15 questions was completed by Belgian pulmonologists (n=31) and European (n=10) COPD experts. RESULTS: Good consensus was reached by both expert groups for long-acting bronchodilators instead of short-acting bronchodilators as first-choice treatment in GOLD A. Single bronchodilation with long-acting muscarinic antagonist (LAMA) was preferred over long-acting ß2-agonist (LABA) and LABA/LAMA as first-choice treatment in GOLD B and GOLD C. For GOLD D patients based on the forced expiratory volume in 1 second (FEV1)<50%, a very good consensus was reached for LAMA/LABA as first-choice treatment. For GOLD D patients based on frequent or severe exacerbations, there was a good consensus for LABA/LAMA/inhaled corticosteroids (ICS) as first choice in the Belgian group. According to the European experts, both LABA/LAMA and LABA/LAMA/ICS could be the first choice for these patients. CONCLUSION: Belgian and European experts recommend long-acting bronchodilators as first-choice treatment. Treatment containing ICS was found only appropriate in patients with FEV1<50% and ≥2 moderate exacerbations or 1 severe exacerbation/year.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Adrenergic beta-2 Receptor Agonists/administration & dosage , Bronchodilator Agents/administration & dosage , Delphi Technique , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenal Cortex Hormones/adverse effects , Adrenergic beta-2 Receptor Agonists/adverse effects , Belgium , Bronchodilator Agents/adverse effects , Consensus , Disease Progression , Drug Combinations , Evidence-Based Medicine , Forced Expiratory Volume , Humans , Lung/physiopathology , Muscarinic Antagonists/adverse effects , Patient Selection , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: In asthma patients, the assessment of activity limitation is based on questions evaluating how limited the patient feels in their activities. However, the lack of functional data complicates the interpretation of the answers. We aimed to evaluate the intensity of relationships between the patient's perception of activity limitation and the results of several functional tests. METHODS: Twenty patients complaining of asthma exacerbation were invited to complete three scores (Chronic Respiratory Disease questionnaire, Asthma Control Questionnaire, Hospital Anxiety and Depression scale). They also underwent lung function measurements, a 6-minute walk test and a cardio-pulmonary exercise test. In addition, physical activity was studied by actigraphy. Spearman's rank correlation coefficients between the patient's perception of activity limitation and each of the other parameters were analysed. RESULTS: Five parameters were significantly correlated with the perception of activity limitation: ACQ question 4, related to dyspnea (rs 0.74, p < 0.001); Emotion domain of the Chronic Respiratory Disease questionnaire (rs -0.57, p = 0.02); HAD anxiety (rs 0.48, p = 0.032); HAD depression (rs 0.46, p = 0.041); ACQ question 6, related to reliever use (rs 0.46, p = 0.046). No parameters from the lung function test, 6MWT, CPET or actigraphy, were significantly correlated with the perception of activity limitation. CONCLUSIONS: In response to questions about limitation of activity, patients do not specifically answer mentioning physical limitation but rather the psychological burden associated with this constraint.