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Introduction: According to Global Initiative for Asthma (GINA) guidelines, long-acting muscarinic antagonists (LAMAs) should be considered as add-on therapy in patients with asthma that remains uncontrolled, despite treatment with medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS)/long-acting β 2 -agonist (LABA) combinations. In patients ≥ 18 years, LAMA may be added in triple combination with an ICS and a LABA. To date, the precise efficacy of triple ICS/LABA/LAMA combination remains uncertain concerning the impact on exacerbation risk in patients with uncontrolled asthma. Therefore, an umbrella review was performed to systematically summarize available data on the effect of triple ICS/LABA/LAMA combination on the risk of asthma exacerbation., Methods: An umbrella review has been performed according to the PRIOR statement., Results: The overall results obtained from 5 systematic reviews and meta-analyses suggest that triple ICS/LABA/LAMA combination reduces the risk of asthma exacerbation. HD-ICS showed a greater effect particularly in reducing severe asthma exacerbation, especially in patients with evidence of type 2 inflammation biomarkers., Conclusions: The findings of this umbrella review suggest an optimization of ICS dose in triple ICS/LABA/LAMA combination, based on the severity of exacerbation and type 2 biomarkers expression.

Objective: Among animals defined as "pests", cockroaches and rodents (mouse and rat) represent the most common cause of airway allergic sensitization and bronchial asthma worldwide. Their frequency of sensitization has been widely assessed in US and other countries but poorly in Western Europe. This narrative review aims to provide a synthesis of data resulting in MEDLINE concerning allergic sensitization/asthma to pests as well as their related environmental/social risk factors, specifically in the European area., Data Sources: We performed a literature research in MEDLINE for clinical trials, randomized controlled trials, systematic reviews and meta-analyses., Study Selections: We selected studies to the following key words: allergic sensitization, allergic rhinitis, bronchial asthma, cockroach, hypersensitivity, integrated pest management, material hardship, medication compliance, mouse, pest, poverty, rat, rodents., Results: Current evidence indicates that residence in poor and urban areas, exposure to outdoor/indoor pollutants and tobacco smoke, poverty, material hardship, poor-quality housing, differences in health care quality, medication compliance, health care access contribute to increased pest-related allergic sensitization and asthma morbidity., Conclusion: Further research should be done on many aspects of pest allergy such as a better characterization of allergens and epidemiological aspects. Relevant social actions should be carried out against poverty, healthcare disparities, psycho-social stress, poor compliance to therapy, with economic contributions to improve private and public living environments. Allergic sensitization to pests and pest-allergic respiratory diseases like asthma are "paradoxical" conditions, as they typically affect the poorest communities but can only be corrected by high-cost (diagnostic and preventive) interventions. We hope that progress can be made in this direction in the future.

Introduction: Advances in understanding the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD) led to investigation of biologic drugs targeting specific inflammatory pathways. No biologics are licensed for COPD while all the approved monoclonal antibodies (mAbs) for severe asthma treatment are systemically administered. Systemic administration is associated with low target tissue exposure and risk of systemic adverse events. Thus, delivering mAbs via inhalation may be an attractive approach for asthma and COPD treatment due to direct targeting of the airways., Areas Covered: This systematic review of randomized control trials (RCTs) evaluated the potential role of delivering mAbs via inhalation in asthma and COPD treatment. Five RCTs were deemed eligible for a qualitative analysis., Expert Opinion: Compared to systemic administration, delivering mAbs via inhalation is associated with rapid onset of action, greater efficacy at lower doses, minimal systemic exposure, and lower risk of adverse events. Although some of the inhaled mAbs included in this study showed a certain level of efficacy and safety in asthmatic patients, delivering mAbs via inhalation is still challenging and controversial. Further adequately powered and well-designed RCTs are needed to assess the potential role of inhaled mAbs in the treatment of asthma and COPD.

Background: The strength of association between comorbidities and asthma has never been ranked in relation to the prevalence of the comorbidity in the nonasthma population. We investigated the strength of association between comorbidities and asthma., Methods: A comprehensive literature search was performed for observational studies reporting data on comorbidities in asthma and nonasthma populations. A pairwise meta-analysis was performed and the strength of association calculated by anchoring odds ratios and 95% confidence intervals with the rate of comorbidities in nonasthma populations via Cohen's d method. Cohen's d= 0.2, 0.5 and 0.8 were cut-off values for small, medium and large effect sizes, respectively; very large effect size resulted for Cohen's d  >0.8. The review was registered in the PROSPERO database; identifier number CRD42022295657., Results: Data from 5 493 776 subjects were analysed. Allergic rhinitis (OR 4.24, 95% CI 3.82-4.71), allergic conjunctivitis (OR 2.63, 95% CI 2.22-3.11), bronchiectasis (OR 4.89, 95% CI 4.48-5.34), hypertensive cardiomyopathy (OR 4.24, 95% CI 2.06-8.90) and nasal congestion (OR 3.30, 95% CI 2.96-3.67) were strongly associated with asthma (Cohen's d >0.5 and ≤0.8); COPD (OR 6.23, 95% CI 4.43-8.77) and other chronic respiratory diseases (OR 12.85, 95% CI 10.14-16.29) were very strongly associated with asthma (Cohen's d >0.8). Stronger associations were detected between comorbidities and severe asthma. No bias resulted according to funnel plots and Egger's test., Conclusion: This meta-analysis supports the relevance of individualised strategies for disease management that look beyond asthma. A multidimensional approach should be used to assess whether poor symptom control is related to uncontrolled asthma or to uncontrolled underlying comorbidities., Competing Interests: Conflict of interest: P. Rogliani participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis, and her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici Novartis, and Zambon, outside the submitted work. Conflict of interest: R. Laitano has nothing to disclose. Conflict of interest: J. Ora has nothing to disclose. Conflict of interest: R. Beasley reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline and Genentech, personal fees from Avillion and Theravance, outside the submitted work. Conflict of interest: L. Calzetta has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis; received nonfinancial support from AstraZeneca; a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall; is or has been a consultant to ABC Farmaceutici, Edmond Pharma, Zambon, Verona Pharma, and Ockham Biotech; and his department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon, outside the submitted work., (Copyright ©The authors 2023.)