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Jérémy Laroche,1 Geneviève Pelletier,1 Marie-Ève Boulay,1 Andréanne Côté,1,2 Krystelle Godbout1,2 1Department of Pulmonology and Thoracic Surgery, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada; 2Department of Medicine, Faculty of Medicine, Laval University, Quebec City, QC, CanadaCorrespondence: Krystelle Godbout, Department of Pulmonology and Thoracic Surgery, Quebec Heart and Lung Institute, 2725 Chemin Sainte-Foy, Quebec, QC, G1V 4G5, Canada, Tel +1 418 656 4747, Fax +1 418 656 4762, Email krystelle.godbout@criucpq.ulaval.caIntroduction: Monoclonal antibodies targeting interleukin 5 (IL5) or its receptor (IL5R) are frequently used in severe asthma, in which they reduce exacerbations rate and oral corticosteroids (OCS) exposure. Anti-IL5/IL5Rs have been studied in patients with chronic obstructive pulmonary disease (COPD) without convincing benefits. However, these therapies have been used in clinical practice in COPD with apparently good results.Purpose: To describe the clinical characteristics and therapeutic response of COPD patients treated with anti-IL5/IL5R in a real-world setting.Patients and Methods: This is a retrospective case series of patients followed at the Quebec Heart and Lung Institute COPD clinic. Men or women, with an established diagnosis of COPD, and treated either with Mepolizumab or Benralizumab were included. Demographics, disease and exacerbation-related data, airway comorbidities, lung function, and inflammatory profile were extracted from patients’ hospital files at baseline visit and 12 months post-treatment. Therapeutic response to biologics was assessed by measuring change in annual exacerbation rate and/or OCS daily dose.Results: Seven COPD patients treated with biologics were identified (5M:2F). All were found to be OCSdependent at baseline. Radiological evidence of emphysema was found in all patients. One case was diagnosed with asthma before age 40. Residual eosinophilic inflammation was found in 5/6 patients (blood eosinophils count 237 ± 225× 106 cells/L) despite chronic OCS use. After 12 months of anti-IL5 treatment, mean OCS dose dropped from 12.0 ± 7.6 to 2.6 ± 4.3 mg/day, representing a 78% decrease. Annual exacerbations rate was reduced by 88%, from 8.2 ± 3.3 to 1.0 ± 1.2 per year.Conclusion: Chronic OCS use is a common characteristic of patients treated with anti-IL5/IL5R biological therapies in this real-world setting. In this population, it may be effective in decreasing OCS exposure and exacerbation.Keywords: COPD, treatment, anti-IL5, monoclonal antibodies, exacerbations, oral corticosteroids

Much interest has been given to the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) in the past 2 decades, but the condition is still ill-defined. There is general agreement that a patient with longstanding asthma who develops fixed airflow obstruction after years of smoking has ACO although defining asthma in the face of COPD can be challenging. Many features of asthma are also found in patients with COPD without indicating an overlap and no consensus exists on which characteristics should be included in the definition of ACO. Nevertheless, some guidance has been issued to help clinicians and researchers to make a diagnosis of ACO and these will be reviewed here.

Thibaud Soumagne, Florence Levesque, Julie Milot, Krystelle Godbout, Yves Lacasse, François Maltais Service de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaCorrespondence: Thibaud SoumagneService de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaEmail thibaud_soumagne@live.frIntroduction: Stenotrophomonas maltophilia is an emerging Gram-negative MDR bacteria. In patients with chronic obstructive pulmonary disease (COPD), it is mostly found in those with severe exacerbation of COPD requiring mechanical ventilation. The significance of S. maltophilia when detected in the sputum of ambulatory patients with COPD is uncertain.Objective: To access the prevalence and the risk factors of the presence of S. maltophilia in the sputum of ambulatory patients with COPD and to determine whether it was associated with prognosis.Methods: All consecutive unselected ambulatory patients with GOLD 2– 4 COPD were recruited between January 2017 and September 2019 from the COPD clinic of a tertiary care hospital. Presence of S. maltophilia was defined by a positive sputum culture for S. maltophilia. Demographics, COPD characteristics, comorbidities and known predisposing risk factors associated with S. maltophilia were collected from medical records.Results: S. maltophilia was detected in the sputum of 41/393 (10%) of study participants. Comorbidities, exacerbation, use of oral steroids and carbapenems in the previous year were risk factors for the presence of S. maltophilia. After adjusting on confounding factors associated with mortality including age, Charlson comorbidity index and FEV1, S. maltophilia was significantly associated with mortality (adjusted hazard ratio 2.3; 95% CI 1.1– 4.9).Conclusion: In the current study, we found that 10% of ambulatory patients with GOLD 2– 4 COPD had S. maltophilia detected in their sputum. In addition, S. maltophilia may represent a marker of overall morbidity in patients with COPD.Keywords: Stenotrophomonas maltophilia, pulmonary disease, chronic obstructive, risk factors, prognosis

To identify susceptibility loci and candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS revealed 72 asthma-associated loci from 116 independent significant variants (PGWAS 20) including a stop-gain mutation in the filaggrin (FLG) gene. The top lung TWAS gene on 17q12-q21 was GSDMB (PTWAS=1.42E-54). Other TWAS genes of interest include TSLP on 5q22, RERE on 1p36, CLEC16A on 16p13, and IL4R on 16p12, which all replicated in GTEx lung (n = 515). A novel risk locus was also revealed by the lung asthma TWAS on 1q23.3 with the putative gene encoding the gamma chain of the high-affinity IgE receptor (FCER1G, PTWAS=2.13E-6), which was also replicated in GTEx lung (PTWAS=3.71E-7). By testing a comprehensive set of cells and tissues, we then demonstrated that the largest fold enrichment of regulatory and functional annotations among asthma-associated variants was in the blood. We mapped 485 eQTL-regulated genes associated with asthma in the blood and 50 of them were shown to be causally associated with asthma by Mendelian randomization. Prioritization of druggable genes revealed known (IL4R, TSLP, IL6, TNFSF4) and potentially new therapeutic targets for asthma.

To identify candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS reveals 72 asthma-associated loci from 116 independent significant variants (PGWAS, Kim Valette et al. perform a genomic study on asthma integrating genome-wide association study, functional mapping using lung and blood transcriptome-wide profiles, as well as Mendelian randomization. They show candidate causal genes expressed in lung and blood tissues that are putative therapeutic targets for asthma.

Asthma is a chronic inflammatory disease of the airways affecting more than 300 million patients worldwide. The disease can be of various severity ranging from very mild to severe. The severe form of the disease only affects about 5% of patients but is responsible for a large component of the overall disease burden and results in about half of direct asthma-related costs. This led to important investments in research, which allowed better understanding of its pathophysiology and the development of new therapeutic strategies. Despite those breakthroughs, recent guidelines still emphasize the need to distinguish uncontrolled or difficult-to-control asthma from severe asthma. Indeed, a significant number of patients referred to severe asthma clinics are non-severe uncontrolled patients. However, the basics of asthma management such as ensuring that the patient has the right diagnosis, recognition of contributing comorbidities, avoidance of exposure to sensitizing agents in allergic individuals, regular assessment of control, and patient education should not be forgotten. The major improvements in pathophysiology arose from the evidences that asthma is of heterogeneous nature. Such heterogeneity has been particularly studied in severe asthma, leading to the recognition of more homogeneous groups referred to as phenotypes. Appropriate phenotyping of individual patients allows enforcing more specific treatment plans for patients, which is a step toward precision medicine. The high morbidity and socioeconomic burden of severe asthma has led to the development of optimized therapeutic strategies in addition to the commercialization of new drugs. Many of these have targeted the eosinophilic component of inflammatory asthma phenotypes while there is still a need to develop new therapies for non-eosinophilic asthma. When asthma is not controlled by optimal therapy, including a high-dose of inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA), a long acting anticholinergic agent can be added and if insufficient, a variety of biologic agents is now available in many countries. When biologics are not an option, thermoplasty and macrolides have also become available. Despite many recent breakthroughs in severe asthma, much research needs to be done. Improvement in availability of targeted asthma medications and asthma prevention should be top priorities.

A 55-year-old former professional athlete reported out of proportion dyspnea on exertion. After a detailed cardiac investigation, a cardiopulmonary exercise test on an ergocycle demonstrated an abnormal and non-physiological ventilatory response characterized by a sharp rise in ventilation followed by a decrease while exercise workload was progressively increasing. This was accompanied by noisy breathing. A laryngoscopy with direct visualisation of larynx and vocal cord during voluntary eucapnic hyperventilation confirmed the diagnosis of exercise-induced laryngeal obstruction. The patient was treated with speech therapy and all the symptoms resolved. A second cardiopulmonary exercise test showed a normalisation of the ventilatory pattern during exercise. This case demonstrates the importance of recognizing the symptoms of an exercise-induced laryngeal obstruction regardless of age, and the effectiveness of the speech therapy on symptoms and on exercise testing. Keywords: Exercise-induced laryngeal obstruction, Stridor, Exercise testing

Breathlessness during sport can be caused by various cardiorespiratory conditions, but when associated with stridor, usually arises from an upper airway etiology. The term exercise-induced laryngeal obstruction (EILO) is now used to describe the phenomenon of transient glottic closure occurring in association with physical activity. Exercise-related laryngeal closure is most commonly encountered in athletic individuals and likely affects between 5% and 7% of all young adults and adolescents. The diagnosis of EILO is not always straightforward because features can overlap with exercise-induced asthma/exercise-induced bronchoconstriction. EILO can therefore remain misdiagnosed for years, and most patients receive inappropriate asthma therapy. In contrast with asthma, EILO symptoms are usually most prominent at maximal exercise intensity and resolve quickly on exercise cessation. It is important to recognize that EILO and asthma can coexist in a proportion of athletes. The criterion standard test for diagnosing EILO is continuous laryngoscopy during exercise testing, although eucapnic voluntary hyperpnea testing has also been used. Various surgical or pharmacological interventions can be used to treat EILO, but first-line treatment is breathing technique work. Further research is needed to establish the optimal treatment algorithm, and more work is needed to increase awareness of this important clinical entity.

Background: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be assessed using registry data, the prevalence of traits in severe and non-severe asthma, and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 with non-severe. Published treatable traits were mapped to registry data fields and their prevalence described. Participants were characterised at baseline and each 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary (7 traits), extrapulmonary (13 traits) and behavioural/risk-factors (4 traits). People with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitisation, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being exacerbation prone (IRR 2.07 (1.66, 2.58), depression (IRR 1.63 (1.31, 1.88), inhaler-device polypharmacy (IRR 1.51 (1.31, 1.75), vocal cord dysfunction (IRR 1.51 (1.22, 1.88) and obstructive sleep apnoea (IRR 1.41 (1.05, 1.89). Conclusion: Treatable traits can be assessed using severe asthma registry data. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating clinical utility of assessing treatable traits.

Background and objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. Conclusion: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Bronchoprovocation tests are used to assess the propensity of the airways to narrow when challenged with a stimulus that induces airway narrowing. The tendency of the airways to respond too much and too easily to various stimuli that induce airway narrowing is called airway hyperresponsiveness (AHR), which is present in asthma, and can also be present in other airway disorders and individuals who are at risk for asthma. Tests of AHR are useful as diagnostic tests for asthma and can reveal useful information about the underlying basis of airway dysfunction. Bronchoprovocation tests are divided into direct tests that provide an exogenous stimulus for bronchoconstriction and indirect tests that rely on the endogenous release of mediators that cause bronchoconstriction. Because direct tests are sensitive to structural changes in the airways and lung, such tests are sensitive to detect the presence of asthma, but are not specific for a diagnosis of asthma. In contrast, indirect tests may reflect the type of inflammation present in asthma and are thus more specific for asthma and most useful to confirm a diagnosis of asthma and to understand the specific basis of asthma symptoms. Bronchoprovocation tests should be interpreted along with clinical features of asthma and other respiratory disorders.

Background: Sampling of peripheral pulmonary nodules with radial endobronchial ultrasound (p-EBUS) increases diagnostic yield of bronchoscopy. However, diagnostic yield is influenced by numerous factors. Objective: We evaluated the use of SpyGlass, a one millimeter diameter optic fiber, to obtain images of the distal mucosa and of pulmonary lesions detected with p-EBUS to determine if visual aspect of the distal mucosa was predictive of diagnosis. Methods: We prospectively recruited subjects investigated for peripheral nodules. Bronchoscopy was performed and p-EBUS was used to locate the lesion through a guide sheath. The Spyglass fiber was introduced in the sheath to obtain images of the distal bronchial mucosa. Tissue sampling was subsequently done. Results: Fifteen patients were enrolled in the study. A final diagnosis of malignancy was confirmed in 80%. All lesions could be located using p-EBUS (100%). Diagnostic sensitivity for p-EBUS was 58.3%. Distal mucosa could be imaged with SpyGlass in 14/15 patients (93.3%). Mucosal appearance was described as abnormal in 7 out of the 15 subjects. Mean SpyGlass procedure time was 6.5 minutes. No direct complication was reported. Conclusion: Spyglass can be used in combination with p-EBUS to obtain images of the distal bronchial mucosa and peripheral pulmonary nodules. More patients will be needed to confirm whether mucosal appearance can be predictive of malignancy.

A combination of opioid, midazolam, and scopolamine (that we call “distress protocol” [DP]) is used to induce transient sedation when emergencies occur in palliative care. We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD). In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed. Thirty patients with cancer and 29 with COPD received at least 1 DP. All patients receiving a DP for an appropriate indication were sedated within 30 minutes. There was no difference in survival from DP administration among patients who received it and those who did not.