Background Tezepelumab is the most recent human monoclonal antibody in the therapeutic arsenal of patients with severe uncontrolled asthma. It neutralizes thymic stromal lymphopoietin (TSLP). Phase 2 and phase 3 studies showed a significant reduction in asthma exacerbations in the severe asthma population, with the greatest effects seen in patients with a type 2 (T2) phenotype. TSLP is in close relation with the epithelium which is believed to be the starting point of the inflammatory cascade. Hence, blocking TSLP is expected to fully control type 2 inflammation and its actors such as interleukin 4 (IL-4), IL-13, IL-5 and eosinophils. This case report describes asthma patient cases with uncontrolled T2 inflammation on tezepelumab and explores the potential evasion mechanisms of TSLP blockage. Cases presentation We report four patients who developed symptomatic uncontrolled T2 inflammation following the initiation to tezepelumab. All cases were biologic-experienced and achieved best asthma control with benralizumab. Several hypotheses have been proposed to explain this phenomenon. One possibility is an immune-driven process within the spectrum of eosinophilic granulomatosis with polyangiitis (EGPA). In EGPA, eosinophils act as immunoregulatory cells and have a critical role in promoting the T2 response, which truly sanction the disease as an eosinophilic immune dysfunction disorder. With such process, targeting upstream signals, such as TSLP may prove ineffective in controlling the self-sustained eosinophilic process. Additionally, local airway immunity, even in the absence of EGPA, could influence the suboptimal response to anti-TSLP therapy by exacerbating the in situ T2 response. Conclusion Tezepelumab is not the optimal treatment for all asthma patients requiring biologic therapy. A non-epithelial derived source of inflammation might explain the suboptimal response. These cases stress the importance of phenotyping and individualisation of therapy as essential steps of the severe asthma care.

BACKGROUND:Because the number of monoclonal antibodies available for severe asthma is growing, specialists currently choose without clear guidelines. Despite increasing knowledge on treatment response to these monoclonal antibodies, making the optimal choice for each individual patient remains a challenge. However, evidence of this daily challenge is lacking. OBJECTIVE:To evaluate interobserver agreement on the choice of biologic therapy in severe asthma patients among severe asthma specialists, based on clinical cases. METHODS:This 2-phase study included a pilot local study and an international validation study. Asthma specialists were presented 7 real-life asthma cases managed with a monoclonal antibody. Based on the clinical information provided in the cases, they were asked whether they would have initiated a monoclonal antibody and, if so, their treatment of choice between (1) omalizumab, (2) mepolizumab, (3) reslizumab, (4) benralizumab, and (5) dupilumab. Interobserver agreement for each question was assessed using Gwet agreement coefficient (AC1). RESULTS:Sixteen physicians from the Province of Quebec (Canada) completed the pilot survey, and 70 physicians from 26 countries completed the international survey. The Gwet AC1 for the decision to initiate a biological therapy was 0.48 in the pilot survey and 0.33 in the international survey. For the choice of therapy, agreement was 0.33 and 0.26, respectively. CONCLUSIONS:The interobserver agreement among asthma specialists in both the decision to initiate a biological treatment in patients with severe asthma and the selection of treatment is weak. These results highlight the need for studies seeking reliable predictors for optimal response to biological therapies.

Background:Chronic cough significantly impacts individuals' quality of life and poses challenges for healthcare providers due to limited licensed treatments, side effects of available medications and difficulty accessing nonpharmacological interventions. Understanding priorities for research, education and knowledge dissemination from the perspectives of individuals with chronic cough and healthcare providers can guide future efforts. This study aimed to identify these key priorities in Canada. Study design and methods:We conducted a cross-sectional study using the James Lind Alliance (JLA) method to set priorities. Chronic cough was identified as the healthcare problem. Participants rated items related to research, education and knowledge dissemination in an online survey using a seven-point Likert scale. Results of the survey were reviewed by the Canadian Thoracic Society's (CTS) multidisciplinary working group and patient partners who engaged in a face-to-face Priority-Setting Partnership, to establish a "Top 10" priorities list for chronic cough. Results:74 individuals with chronic cough and 62 healthcare providers completed the scoping survey. The top-rated priorities included enhancing knowledge of existing treatments, developing new treatments and improving diagnostic testing. The final "Top 10" priorities list emphasised the need for developing infrastructure for evaluating new treatments, improving understanding of biological mechanisms and raising awareness among the public and policymakers. Conclusion:This is the first priority-setting project for chronic cough, highlighting key areas to address in research, education and dissemination. The identified priorities will serve as a foundation for future efforts to improve the management and care of individuals with chronic cough.

Rationale. Oral corticosteroids (OCS) are the mainstay of treatment for severe asthma exacerbation, but some patients do not seem to benefit from them. This can be attributed to a misdiagnosis as many exacerbations are not confirmed with objective tests. It is also possible that a number of exacerbations are not T2-driven and may not require OCS treatment, but this hypothesis has not been validated. Studies using a comprehensive assessment of exacerbations leading to personalized management approaches are lacking. Aim. To compare the characteristics and outcomes of patients treated or not with OCS following a systematic assessment of their exacerbation. Methods. This study is part of a real-life interventional cohort study on optimizing the management of asthma exacerbation. Adult patients with severe asthma presenting symptoms of an exacerbation were recruited for a complete assessment that included pulmonary function tests, blood tests, induced sputum analysis and FeNO measurement. Then, a respirologist confirmed the exacerbation and decided on a treatment plan, which could include OCS. A follow-up call was performed 14 days later to assess outcomes. T2 exacerbations were defined as ≥1 of the following: FeNO ≥25 ppb, sputum eosinophils ≥2%, blood eosinophils ≥300 cells/uL. FEV1 <80% of personal's best was also considered a possible requirement for OCS. Unfavorable outcome was defined as either an initiation or prolongation of antibiotics and/or OCS, or a re-consultation (unplanned medical visit or emergency room visit). Results. We included 66 patients (34 (52%) women, mean (range) age 61 (19-83) years old), of whom 7 came twice, for a total of 73 visits analysed. Of these, 25/73 visits (34%) resulted in OCS prescription. A T2 profile and/or an FEV1 <80% of the personal's best was seen in 18/25 (72%) of the OCS-treated patients and 22/48 (46%) of those not treated with OCS. Unfavorable outcome was reported by 5/25 (20%) patients in the OCS-treated group, 3 of them (60%) presented a T2 profile. In the non-OCS group, 18/48 (38%) visits ended up with an unfavorable outcome, of which 9 (50%) showed a T2 profile. Conclusion. The decision of how to treat severe asthma exacerbations is, to some extent, influenced by the presence of a T2 profile and/or fall in FEV1 but also by other factors possibly related to heterogeneity in the decision process of physicians involved in the study. This reflects the lack of standardized guidelines and the need for a more tailored approach to managing asthma exacerbations.

Rationale: Nasal polyposis is a comorbidity of asthma that is associated with type 2 inflammation. Non-invasive biomarkers of type 2 inflammation, particularly fractional exhaled nitric oxide (FeNO), have been proposed as potentially useful in predicting the presence of nasal polyposis. In this study, we evaluated the ability of inflammatory biomarkers to identify patients with a history of nasal polyposis among patients with asthma. Methods: We analyzed data from the OxfoRd Asthma attaCk risk scaLE (ORACLE2) patient-level meta-analysis (PROSPERO: CRD42021245337), which includes 6,513 participants from 22 Randomized Controlled Trials (RCTs) investigating the effects of fixed treatment regimens on severe asthma exacerbation rates over a minimum of 24 weeks. In a complete case analysis, we included patients with data on nasal polyposis history (any mention or timing of nasal polyposis or previous nasal polypectomy in comorbidity list) and inflammatory biomarkers (FeNO, blood eosinophil count (BEC), and serum immunoglobulin E (IgE)). We then evaluated the ability of each inflammatory biomarker to identify patients with a history of nasal polyposis by calculating the Area Under the Curve (AUC) using Receiver Operating Characteristic (ROC) analysis. RESULTS: We included 4,165 patients from 15 RCTs, with n=598 (14%) reporting nasal polyposis. The analysis population comprised moderate-to-severe asthma (n=1,265 severe). Data were available for FeNO (n=3,884), BEC (n=4,120), and IgE (n=4,110). The performance of FeNO and BEC in identifying a history of nasal polyposis was poor, with AUC values of 0.62 [0.59; 0.64] and 0.62 [0.59; 0.64], respectively. For FeNO ≥ 74 ppb, specificity attained 90% [95% CI 89-91] and for BEC ≥ 0.61x109/L, specificity attained 90% [95% CI 89-91]. For both these cut-offs, sensitivity was very low (< 22%) and the positive likelihood ratio (PLR) was insufficient to identify nasal polyposis (PLR <10: FeNO ≥ 73 ppb, PLR=1.7; BEC ≥ 0.61x109/L, PLR=2.2). Furthermore, IgE was not a discriminative biomarker for nasal polyposis (AUC: 0.50 [0.48; 0.52]) CONCLUSION: Biomarkers (FeNO, BEC, IgE) are not features accurately distinguishing patients with asthma reporting a history of nasal polyposis and those who do not. These results suggest that type-2 biomarkers are not substantially affected by the presence of nasal polyposis. REGISTRATION: PROSPERO-CRD42021245337

BACKGROUND:Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes.METHODS:The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management.RESULTS:The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent.CONCLUSIONS:Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved.

AbstractDespite the widespread use of vaping, a very limited number of clinical studies have investigated the effects of this habit on the lungs of healthy individuals. Our group recently initiated theVapingAdverseLung and HeartEvents Cohort(VapALERT), a prospective study aiming to identify the impacts of vaping on respiratory and cardiovascular health. We elected to report early findings from the pulmonary function tests performed at the initial visit of the first 83 participants recruited so far. Almost 80% of volunteers with no diagnosis of lung disease and who vape daily have an abnormal airway reactivity to metacholine and/or lung clearance index and/or diffusion capacity. We can conclude from this study that adult individuals who vape daily are very likely to present asymptomatic functional respiratory abnormalities, especially airway hyperresponsiveness, ventilation heterogeneity and reduced gas diffusion regardless of past or current tobacco and/or cannabis smoking. Longitudinal studies are crucial to determine how respiratory abnormalities observed in individuals who vape will progress over time.

Introduction: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.

Introduction: Bronchial thermoplasty is an effective intervention for reducing respiratory symptoms and exacerbations in uncontrolled asthma. A reduction in airway smooth muscle (ASM) is thought to account for these clinical benefits. Yet, an ASM reduction should also translate into an impaired response to bronchodilator drugs. Objective: Investigate whether thermoplasty decreases the response to a bronchodilator. Methods: Respiratory mechanics measured by oscillometry were examined pre- and post-bronchodilator (salbutamol, 400 µg) before and after at least 1 year of thermoplasty in 8 patients (7 women) with uncontrolled severe asthma. The IUCPQ Ethics Committee approved the project, and two-way ANOVAs were used to assess the effect of thermoplasty, salbutamol, and their interaction. Results: Despite improving symptoms based on asthma control questionnaires, thermoplasty yielded no benefits in terms of baseline respiratory mechanics. However, a significant interaction was observed between thermoplasty and salbutamol for 2 oscillometric readouts. The reactance of the respiratory system at 5 Hz (Xrs5) increased from -3.2 ± 2.6 to -1.9 ± 1.9 cmH2O·s/L in response to salbutamol pre-thermoplasty, versus from -2.8 ± 2.3 to -2.2 ± 1.9 cmH2O·s/L post-thermoplasty (interaction, p=0.04). Similarly, the reactance area (Ax) decreased from 32.6 ± 29.0 to 12.8 ± 18.2 cmH2O/L in response to salbutamol pre-thermoplasty, versus 27.2 ± 29.4 to 15.7 ± 20.1 cmH2O/L post-thermoplasty (interaction, p=0.02). Conclusion: These results suggested that thermoplasty attenuates the bronchodilator response, representing a physiological evidence of therapeutic efficacy in line with the effect of thermoplasty in reducing ASM.

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. Methods A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient (kappa) value > 0.61. Results After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. Conclusion This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

A significant number of patients with asthma have poor control on their current inhaled therapies, typically a combination of inhaled corticosteroids (ICS) and long-acting beta-2 adrenergic bronchodilators (LABA). Adding a long-acting antimuscarinic agent (LAMA) has been shown to improve asthma control and the availability of triple therapy formulations (ICS/LABA/LAMA) in a single inhaler device or single inhaler triple therapy (SITT) mitigates the adherence concerns associated with use of multiple inhaler devices. Here, we provide an overview of the pivotal data concerning the use of triple asthma therapy in patients with poor control on ICS-LABA treatment, and present our expert approach to their application in the routine clinical management of such patients as well the appropriate sequencing of initiating triple therapy and seeking a referral for consideration of more advanced therapies.

Objective: Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in airway smooth muscle is arguably the most widely discussed mechanisms accounting for these clinical benefits. Yet, this smooth muscle reduction should also translate into an impaired response to bronchodilator drugs. A pilot study was designed to address this question. Hypothesis: Thermoplasty decreases the response to a bronchodilator. Methods: Lung functions measured by spirometry and respiratory mechanics measured by oscillometry (tremoFlo, Thorasys) were examined pre- and post-bronchodilator (salbutamol, 400 μg) before and after at least 1 year of thermoplasty in 8 patients (7 women) with uncontrolled severe asthma. For each readout, a two-way ANOVA was used to assess the effect of thermoplasty, salbutamol, and their interaction. All procedures were approved by the IUCPQ Ethics Committee. Data: Consistent with previous studies, thermoplasty yielded no benefits in terms of baseline lung function and respiratory mechanics, despite improving symptoms based on two questionnaires assessing the level of asthma control (Asthma Control Questionnaire – ACQ-5, and Asthma Control Test – ACT-5). The response to salbutamol was not affected by thermoplasty based on spirometric readouts, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. However, a significant interaction was observed between thermoplasty and salbutamol for two oscillometric readouts. The reactance of the respiratory system at 5 Hz (Xrs5) increased from -3.2 ±2.6 to -1.9 ± 1.9 cmH2O ·s/L in response to salbutamol pre-thermoplasty, versus from -2.8 ± 2.3 to -2.2 ± 1.9 cmH2O·s/L post-thermoplasty (interaction, p=0.04). Similarly, the reactance area (Ax) decreased from 32.6 ± 29.0 to 12.8 ±18.2 cmH2O/L in response to salbutamol pre-thermoplasty, versus 27.2 ± 29.4 to 15.7 ± 20.1 cmH2O/L post-thermoplasty (interaction, p=0.02). The salbutamol-induced changes in resistance at 5 Hz (Rrs5), resistance at 19 Hz (Rrs19), Rrs5 minus Rrs19, and resonant frequency were not significantly affected by thermoplasty. Summary of results: While spirometry was unable to detect changes in the response to salbutamol caused by thermoplasty, two oscillometric readouts, namely Xrs5 and Ax, confirmed that the bronchodilator response is attenuated post-thermoplasty. Conclusion: Despite its small size, this study demonstrates that thermoplasty attenuates the response to a bronchodilator. We argue that this result is a physiological proof of therapeutic efficacy, consistent with the well-described effect of thermoplasty in reducing the amount of airway smooth muscle. FQSR (Fondation Quebecoise en Sante Respiratoire); Canadian Institutes of Health Research (PJT-387910); FRQS (Fonds de recherche du Quebec - Sante); and Boston Scientific Inc This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression, cytokine production and metabolic profile. Despite these observations, biological mechanisms explaining asthma control improvement post-BT are still not well understood. To assess whether BT affects gene signatures in bronchial epithelial cells (BECs). In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment. Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human β-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33. These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.

Introduction: Bronchial thermoplasty (BT), an endobronchial procedure consisting in radiofrenquency delivery of thermal energy in the airways, is a non-pharmacological alternative offered to uncontrolled severe asthmatics. This approach has been associated with better asthma control and reduced exacerbations. However, biological mechanisms explaining asthma control improvement following BT are still not well understood. Our group performed transcriptomic analysis on bronchial epithelial cells (BEC) obtained from severe asthmatic subjects before and one-year after BT treatment. We found a significant gene expression decrease in S100 family of alarmins. Objective: validation of S100A7/A8/A9 expression in bronchial biopsies obtained from severe patients before and one-year post BT and evaluation of S100A7/A8/A9 in BEC from these patients. Method: BEC and biopsies were collected from severe asthmatics before as well as one year after BT. These were compared to BEC isolated from participants without asthma and allergy. S100A7/A8/A9 gene expression was evaluated by qPCR and proteins by Western blot and immunohistochemistry. Results: S100A7/A8/A9 are highly expressed in BEC and bronchial biopsies obtained from severe asthma compared to healthy controls. BT treatment of severe asthmatics showed a significant decrease in S100A7/A8/A9 at gene and protein level in epithelial cells and in bronchial biopsies. This decrease was observed one-year post BT. Conclusion: BT induces a significant decrease in alarmine expression in severe asthmatics which could contribute to better asthma control.

Purpose:Monoclonal antibodies targeting interleukin-5 (IL5) and its receptor (IL5R), used for severe asthma treatment, reduce eosinophils to almost complete depletion. Fractional exhaled nitric oxide (FeNO), a surrogate marker of eosinophilic airway inflammation, is expected to decrease after their initiation. Our center noticed increased FeNO levels in a few patients in whom anti-IL5/IL5R therapy was initiated. Limited data are available on the kinetics of T2 inflammation biomarkers after initiation of a biologic in that population. This study aims to identify if a subgroup of severe asthma patients experiences increased FeNO levels after initiation of anti-IL5/IL5R therapy and to describe their clinical characteristics.Patients and Methods:This is a retrospective case series of 5 patients on Benralizumab (4M:1F) and 8 on Mepolizumab (5M:3F) who showed a significant increase in FeNO (>20% AND >25 ppb) following initiation of an anti-IL5/IL5R treatment. Clinical data, expiratory flows, and inflammation were extracted from the patients' chart at initiation of treatment (T0), 3 months (T1) and 12 months (T2) post-treatment. Descriptive statistics were used.Results:In patients treated with Benralizumab, the increase in FeNO was observed between T0 and T1 (mean delta = 82 ± 72 ppb) with a subsequent decrease (N = 3). In most patients taking Mepolizumab (N = 6), the FeNO increase was observed between T1 and T2 (mean delta = 57 ± 35 ppb). Under treatment, no Benralizumab patient experienced asthma exacerbation while two on Mepolizumab did. All patients had a significant decrease in blood eosinophils.Conclusion:Although initiation of anti-IL5/IL5R may cause a transient rise in FeNO levels in a subgroup of patients, it does not appear to affect clinical outcomes. A compensatory mechanism involving other inflammatory pathways such as IL13 or IL4, both involved in FeNO production, could theoretically explain these findings. Further investigation is needed to elucidate the actual underlying mechanisms.

Although there is still no consensus on the definition of Asthma-COPD Overlap (ACO), it is generally accepted that some patients with airway disease have features of both asthma and COPD. Just as its constituents, ACO consists of different phenotypes, possibly depending on the predominance of the underlying asthma or COPD-associated pathophysiological mechanisms. The clinical picture is influenced by the development of airway inflammatory processes either eosinophilic, neutrophilic or mixed, in addition to glandular changes leading to mucus hypersecretion and a variety of other airway structural changes. Although animal models have exposed how smoking-related changes can interact with those observed in asthma, much remains to be known about their interactions in humans and the additional modulating effects of environmental exposures. There is currently no solid evidence to establish the optimal treatment of ACO but it should understandably include an avoidance of environmental triggers such as smoking and relevant allergens. The recognition and targeting of "treatable traits" following phenotyping is a pragmatic approach to select the optimal pharmacological treatment for ACO, although an association of inhaled corticosteroids and bronchodilators is always required in these patients. This association acts both as an anti-inflammatory treatment for the asthma component and as a functional antagonist for the airway remodeling features. Research should be promoted on well phenotyped subgroups of ACO patients to determine their optimal management.

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INTRODUCTION: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.