Risks of infection, hospital and ICU admission, and death from COVID-19 in people with asthma: systematic review and meta-analyses

ObjectivesTo determine if and to what degree asthma may predispose to worse COVID-19 outcomes in order to inform treatment and prevention decisions, including shielding and vaccine prioritisation.DesignSystematic review and meta-analysis.SettingElectronic databases were searched (October 2020) for clinical studies reporting at least one of the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, intensive care unit (ICU) admission or mortality with COVID-19.ParticipantsAdults and children who tested positive for or were suspected to have COVID-19.Main outcome measuresMain outcome measures were the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, ICU admission or mortality with COVID-19. We pooled odds ratios (ORs) and presented these with 95% confidence intervals (CI). Certainty was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).Results30 (n=112 420) studies were included (12 judged high quality, 15 medium, 3 low). Few provided indication of asthma severity. Point estimates indicated reduced risks in people with asthma for all outcomes, but in all cases the evidence was judged to be of very low certainty and 95% CIs all included no difference and the possibility of increased risk (death: OR 0.90, 95% CI 0.72 to 1.13, I2=58%; hospitalisation: OR 0.95, 95% CI 0.71 to 1.26; ICU admission: OR 0.96, 95% CI 0.75 to 1.24). Findings on hospitalisation are also limited by substantial unexplained statistical heterogeneity. Within people with asthma, allergic asthma was associated with less COVID-19 risk and concurrent chronic obstructive pulmonary disease was associated with increased risk. In some studies, corticosteroids were associated with increased risk, but this may reflect increased risk in people with more severe asthma.ConclusionsThough absence of evidence of a clear association between asthma and worse outcomes from COVID-19 should not be interpreted as evidence of absence, the data reviewed indicate that risks from COVID-19 in people with asthma, as a whole, may be less than originally anticipated.

Identification of Persons Who Are Responsive To Wood Smoke Particle-Induced Airway Inflammation With Assessment of The Effect of GSTM1, Asthma Status And Sex On This Response.

Background: We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6 and 24 hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (>10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (N=52) at both 6 and 24hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP. Results: In the entire cohort, we found a significant, but very small, decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased at 24 hours post exposure, the latter finding was also significantly correlated with sputum IL-1b, IL-6, IL-8, and PMN/mg; a similar response was not found at the 6 hour %PMN response. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1b, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (p<0.05) enhanced the %PMN response at 6 hours in the entire cohort, by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the entire cohort and in the 6- and 24-hour responders. Sex had no effect on %PMN response. Conclusions: The 24 hour time point was more informative than the 6 hour time point in optimally defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.

The Asthma Family Tree: Evaluating Associations Between Childhood, Parental, and Grandparental Asthma in Seven Chinese Cities

Objective: To evaluate the associations between childhood, parental, and grandparental asthma.Methods: We studied 59,484 children randomly selected from 94 kindergartens, elementary, and middle schools in seven Chinese cities from 2012 to 2013, using a cross-sectional survey-based study design. Information on their and their family members' (parents, paternal grandparents, and maternal grandparents) asthma status were reported by children's parents or guardians. Mixed effects logistic regressions were used to assess hereditary patterns of asthma and mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and childhood asthma.Results: The magnitude of ORs for childhood asthma increased as the number of family members affected by asthma increased. Among children who had one family member with asthma, childhood asthma was associated with asthma in maternal grandmothers (OR: 2.08, 95% CI: 1.67–2.59), maternal grandfathers (OR: 2.08, 95% CI: 1.71–2.53), paternal grandmothers (OR: 2.40, 95% CI: 1.93–2.99), and paternal grandfathers (OR: 2.59, 95% CI: 2.14–3.13). Among children who had two family members with asthma, the highest asthma risk was found when both parents had asthma (OR: 15.92, 95% CI: 4.66–54.45). Parents had a small proportion of mediation effect (9–12%) on the association between grandparental asthma and childhood asthma.Conclusions: Grandparents with asthma were associated with childhood asthma and parents with asthma partially mediated the association.

Metabolomic differences in lung function metrics: evidence from two cohorts

RationaleThe biochemical mechanisms underlying lung function are incompletely understood.ObjectivesTo identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery—the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk, n=10 460) and validation—the VA Normative Aging Study (NAS) metabolomic cohort (n=437).MethodsWe ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC), in EPIC-Norfolk then validated significant findings in NAS. Significance in EPIC-Norfolk was denoted using an effective number of tests threshold of 95%; a metabolite was considered validated in NAS if the direction of effect was consistent and p<0.05.Measurements and main resultsOf 156 metabolites that associated with FEV1 in EPIC-Norfolk after adjustment for age, sex, body mass index, height, smoking and asthma status, 34 (21.8%) validated in NAS, including several metabolites involved in oxidative stress. When restricting the discovery sample to men only, a similar percentage, 18 of 79 significant metabolites (22.8%) were validated. A smaller number of metabolites were validated for FEV1/FVC, 6 of 65 (9.2%) when including all EPIC-Norfolk as the discovery population, and 2 of 34 (5.9%) when restricting to men. These metabolites were characterised by involvement in respiratory track secretants. Interestingly, no metabolites were validated for both FEV1 and FEV1/FVC.ConclusionsThe validation of metabolites associated with respiratory function can help to better understand mechanisms of lung health and may assist the development of biomarkers.

Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. Objective The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. Methods Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab–placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). Results Adjusted mean difference (95% CI) (omalizumab–placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. Conclusion Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. Clinical Trial Registration ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 ( https://clinicaltrials.gov/ct2/show/NCT03280550 ); POLYP 2: ClinicalTrials.gov identifier NCT03280537 ( https://clinicaltrials.gov/ct2/show/NCT03280537 ).

Exposure to traffic-related air pollution and bacterial diversity in the lower respiratory tract of children

Background Exposure to particulate matter has been shown to increase the adhesion of bacteria to human airway epithelial cells. However, the impact of traffic-related air pollution (TRAP) on the respiratory microbiome is unknown. Methods Forty children were recruited through the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal cohort followed from birth through early adolescence. Saliva and induced sputum were collected at age 14 years. Exposure to TRAP was characterized from birth through the time of sample collection using a previously validated land-use regression model. Sequencing of the bacterial 16S and ITS fungal rRNA genes was performed on sputum and saliva samples. The relative abundance of bacterial taxa and diversity indices were compared in children with exposure to high and low TRAP. We also used multiple linear regression to assess the effect of TRAP exposure, gender, asthma status, and socioeconomic status on the alpha diversity of bacteria in sputum. Results We observed higher bacterial alpha diversity indices in sputum than in saliva. The diversity indices for bacteria were greater in the high TRAP exposure group than the low exposure group. These differences remained after adjusting for asthma status, gender, and mother’s education. No differences were observed in the fungal microbiome between TRAP exposure groups. Conclusion Our findings indicate that exposure to TRAP in early childhood and adolescence may be associated with greater bacterial diversity in the lower respiratory tract. Asthma status does not appear to confound the observed differences in diversity. These results demonstrate that there may be a TRAP-exposure related change in the lower respiratory microbiota that is independent of asthma status.