Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement.

peer reviewedOBJECTIVES: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD). METHODS: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated. RESULTS: Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus). CONCLUSIONS: The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided

Eosinophils and Lung Cancer: From Bench to Bedside.

peer reviewedEosinophils 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

The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

Background: Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design: Patients with COPD, hospitalized for an AE, who have a smoking history of > 10 pack-years and had > 1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion: We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs

Severe asthma: oral corticosteroid alternatives and the need for optimal referral pathways

Peer reviewe

Rehabilitation in patients with radically treated respiratory cancer: A randomised controlled trial comparing two training modalities.

INTRODUCTION: The evidence on the effectiveness of rehabilitation in lung cancer patients is limited. Whole body vibration (WBV) has been proposed as an alternative to conventional resistance training (CRT). METHODS: We investigated the effect of radical treatment (RT) and of two rehabilitation programmes in lung cancer patients. The primary endpoint was a change in 6-min walking distance (6MWD) after rehabilitation. Patients were randomised after RT to either CRT, WBVT or standard follow-up (CON). Patients were evaluated before, after RT and after 12 weeks of intervention. RESULTS: Of 121 included patients, 70 were randomised to either CON (24), CRT (24) or WBVT (22). After RT, 6MWD decreased with a mean of 38m (95% CI 22-54) and increased with a mean of 95m (95% CI 58-132) in CRT (p<0.0001), 37m (95% CI -1-76) in WBVT (p=0.06) and 1m (95% CI -34-36) in CON (p=0.95), respectively. Surgical treatment, magnitude of decrease in 6MWD by RT and allocation to either CRT or WBVT were prognostic for reaching the minimally clinically important difference of 54m increase in 6MWD after intervention. CONCLUSIONS: RT of lung cancer significantly impairs patients' exercise capacity. CRT significantly improves and restores functional exercise capacity, whereas WBVT does not fully substitute for CRT

Safety of denervation following targeted lung denervation therapy for COPD:AIRFLOW-1 3-year outcomes

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

Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - A post-hoc analysis of the BACE randomized controlled trial

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. © 2019 The Author(s)

A belgian survey on the diagnosis of asthma– COPD overlap syndrome

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 /=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

European Lung Cancer Working Party Clinical Practice Guidelines Non-small Cell Lung Cancer: II. Unresectable Non-metastatic Stages

The present guidelines on the management of unresectable non-metastatic non-small cell lung cancer (NSCLC) were formulated by the ELCWP in October 2005. They are designed to answer the following eight questions: 1) Is chest irradiation curative for NSCLC? 2) What are the contra-indications (anatomical or functional) to chest irradiation? 3) Does the addition of chemotherapy add an advantage to radiotherapy? 4) Does the addition of radiotherapy add an advantage to chemotherapy? 5) Is irradiation as effective as surgery for marginally resectable stage III? 6) How to best combine chemotherapy with radiotherapy: sequentially, concomitantly, as consolidation, as induction, as radiosensitiser? 7) In case of too advanced locoregional disease, is there a role for consolidation (salvage) local treatment (surgery or radiotherapy) after induction chemotherapy? 8) In 2005, what are the technical characteristics of an adequate radiotherapy