Comorbid Asthma Research Articles

Primary antibody deficiencies represent an underestimated comorbidity in asthma patients: efficacy of immunoglobulin replacement therapy in asthma control

Objective Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. Methods a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. Results 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. Conclusions low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD.

Symptom burden and health-related quality of life in moderate to severe chronic rhinosinusitis with nasal polyposis

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) affects up to 4% of individuals. Common symptoms include nasal congestion/obstruction, nasal discharge, facial pain, and reduced sense of smell. This study describes patient- and physician-reported CRSwNP symptom burden and health-related quality of life (HRQOL) in a real-world clinical setting. Methods: This multinational, geographically diverse, point-in-time survey invited physicians to evaluate 5 consecutive adults with confirmed bilateral moderate to severe CRSwNP (consecutive sampling) plus the next 2 patients with recurrent nasal polyps and ≥1 surgery for polyp removal (oversampling). Patients’ and physicians’ surveys were assessed in the entire consecutive sample and by categories of physician-determined CRSwNP severity, and by categories of asthma comorbidity (total sample). Patients’ and physicians’ responses were compared in a matched sample. Results: The total sample of 1,782 patients comprised 1,296 (72.7%) from consecutive sampling and 486 (27.3%) from oversampling. Among the consecutive sample (mean age, 46.9 years), 1,122 (86.6%) had moderate and 174 (13.4%) had severe CRSwNP. Of 1,697 patients from total sampling with known asthma status, 708 (41.7%) had asthma and 989 (58.3%) did not. Patients’ self-reported symptom frequency, severity, and burden on HRQOL worsened with increasing CRSwNP severity and comorbid asthma. Physicians underreported prevalence, severity, and impact of symptoms on daily activities compared with patients (matched sample). Conclusion: Patients and physicians from real-world settings both described a considerable burden of CRSwNP, but physicians consistently reported fewer and less severe symptoms than patients. This suggests a more patient-centric view is needed when assessing CRSwNP symptom burden and HRQOL.

The burden of chronic rhinosinusitis with nasal polyps and its relation to asthma in Finland.

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with asthma. Treatment of CRSwNP includes intranasal and systemic corticosteroids, with non‐responsive patients commonly considered for endoscopic sinus surgery (ESS). This nationwide register‐based study evaluated the incidence, prevalence, and treatment burden of CRSwNP in Finland, and their association with the presence and severity of comorbid asthma.MethodsElectronic health records of patients diagnosed with CRSwNP between 1.1.2012 and 31.12.2018 in Finnish specialty and primary care were included in the study. The patients were divided into subgroups based on presence, severity, and control of asthma: no asthma, mild to moderate asthma, severe controlled asthma, and severe uncontrolled asthma. A mean cumulative count of ESS was calculated over time per subgroup.ResultsThe prevalence of CRSwNP increased from 602.2 to 856.7 patients per 100,000 population between years 2012 and 2019 (p < 0.001). A total of 18,563 patients (59.9% male) had incident CRSwNP between 2012 and 2019, with 27% having asthma, 6% having severe asthma, and 1.5% having severe uncontrolled asthma. In the no asthma, severe controlled asthma, and severe uncontrolled asthma subgroups, systemic corticosteroids were used by 54.1%, 94.9% and 99.3% (p < 0.001), respectively, while the ESS count 3 years post diagnosis was 0.49, 0.68 and 0.80, respectively.ConclusionsThe prevalence of CRSwNP showed a significant increase in the recent decade in Finland. Comorbid asthma, and in particular severe asthma, increased the probability of receiving systemic corticosteroids and undergoing ESS. Thus, improved management of CRSwNP in patients with comorbid asthma is urgently needed.

Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma

BackgroundThe coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma.MethodsTwo sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury.ResultsWe discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein–protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor–gene interactions, DEG–microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes.ConclusionWe identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.

Evaluation of the involvement of PPARG2 gene rs1801282 polymorphism in the pathogenesis of bronchial asthma with obesity in children

Introduction. Features of the clinical course of bronchial asthma in children with obesity made it possible to identify a special phenotype, when the presence and severity of obesity determine a more severe course of asthma and a worse response to asthma therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. Studying the genetic basis of both of these complex traits and linking them to the asthma phenotype should contribute to our understanding of the overall genetic basis of these pathological disorders.Aim. Evaluation of the clinical and genetic significance of the rs1801282 polymorphism of the PPARG2 gene (34C&gt;G, p.Pro12Ala) in children with asthma and obesity.Materials and methods. 161 children with asthma were examined, including 59 patients with obesity 1-3 degrees. The examination included general clinical, functional, instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The study of gene polymorphisms was carried out by the real-time polymerase chain reaction.Results. An analysis of the frequencies of the PPARG2 gene polymorphism in children with bronchial asthma did not reveal any differences from the control group healthy people. In 61% of children with asthma and obesity, there was no control over the disease, which was associated with the G allele (OR 2.4 [95% CI: 1.09‒5.30], p=0.0281). An increase in the activity of lactate dehydrogenase and a decrease in the membrane potential of mitochondria in peripheral blood lymphocytes in children with the GG genotype were revealed, which may indirectly affect the level of disease control.Conclusion. The comorbidity of asthma and obesity in children affects the control of the disease. This manifests itself through immune mechanisms that play a key role in energy homeostasis and mitochondrial dysfunction of immunocompetent blood cells. The G-allele of the PPARG2 gene can be a marker of the lack of control over the disease in obese children with asthma. The pathogenetic significance of this polymorphism requires further study.

Patients with obstructive sleep apnea are at great risk of flavor disorders: a 15-year population-based cohort study.

Obstructive sleep apnea (OSA) results from upper airway remodeling, which has been suggested to alter sensory and motor neuron function due to hypoxia or snore vibration. This study investigated whether OSA was associated with the risk of flavor disorder (FD). Seven thousand and eight hundred sixty-five patients with OSA and 7865 propensity score-matched controls without OSA were enrolled between 1999 and 2013 through a nationwide cohort study. The propensity score matching was based on age, sex, comorbidities including hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), asthma, ankylosing spondylitis, and Charlson comorbidity index, and co-medications during the study period, including statins and angiotensin-converting enzyme (ACE) inhibitors. The adjusted hazard ratio (aHR) of incident FD following OSA was derived using a Cox proportional hazard model. A log-rank test was used to evaluate the time-dependent effect of OSA on FD. Age, sex, comorbidities, and co-medications were stratified to identify subgroups susceptible to OSA-associated FD. Patients with OSA were at a significantly great risk of FD (aHR = 1.91, 95% CI = 1.08-3.38), which was time-dependent (log-rank test p = 0.013). Likewise, patients with hyperlipidemia were at a significant great risk of FD (aHR = 2.99, 95% CI = 1.33-6.69). Subgroup analysis revealed that female patients with OSA were at higher risks of FD (aHR = 2.39, 95%CI = 1.05-5.47). Patients with OSA were at significantly great risk of incident FD during the 15-year follow-up period, especially in female patients with OSA. Timely interventions for OSA may prevent OSA-associated FD.

Association between long-term exposure to air pollution and rhinitis and asthma comorbidities in the Constances cohort

Association between long-term exposure to air pollution and rhinitis and asthma comorbidities in the Constances cohort

Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study.

Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs’ specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.

Risk factors associated with comorbid asthma in patients with chronic rhinosinusitis with nasal polyps: a cross-sectional study

BackgroundAlthough 20–60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients.MethodsThis report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named “modelling” group and “validation” group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group.ResultsTotally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; P < 0.001), allergic rhinitis (OR = 2.9; P = 0.021), serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L (OR = 12.0; P < 0.001), and blood eosinophil count ≥ 0.35 × 109/L (OR = 4.0; P = 0.001) were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA (Kappa = 0.513, P < 0.001), with sensitivity 76.9% and specificity 74.4%.ConclusionsFemale gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients.

Characterisation of patients with chronic obstructive pulmonary disease initiating single-device inhaled corticosteroids/long-acting β2-agonist dual therapy in a primary care setting in England

IntroductionTreatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-device dual therapies in England remain unclear. This study describes the characteristics of patients with COPD before initiating treatment...

33843 Atopic dermatitis polypharmacy and out-of-pocket health care expenses in the United States

Background: Atopic dermatitis (AD) out-of-pocket (OOP) expenses are substantial and impact household finances. Prescription polypharmacy and its association with out-of-pocket (OOP) expenses in AD is poorly understood. Objective: To characterize prescription polypharmacy and its association with OOP health care expenses among individuals with AD. Methods: An online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (U.S. resident, age ≥18, self-reported or caregiver of individual with AD) was met by 77.3% (1118/1447) of respondents. Results: Polypharmacy (≥5 prescription treatments for AD in the past year) was associated with increased AD severity, poorer control, increased flares, increased healthcare provider visits (HCP), and comorbid asthma, allergic rhinitis, food allergy, and skin infections (P ≤ .01). Polypharmacy was also associated with biologic (dupilumab), oral immunosuppressant (azathioprine, cyclosporine, methotrexate, corticosteroids), oral antimicrobial, and topical calcineurin inhibitor use (P ≤ .0005). Respondents with polypharmacy had increased OOP expenditures across numerous categories including office visit co-pays, prescription medications both covered and not covered by insurance, hospitalization, emergency room visits, mental health services, non-prescription health products such as sleep aids, analgesics, and supplements, and alternative medications (P < .005). Individuals with polypharmacy had elevated yearly OOP expenses (median [range]: $1200 [$0-$200,000]), higher monthly OOP costs, and more harmful household financial impact (P < .0001 for all). Similar results were observed with a less stringent definition of polypharmacy (≥3 prescription treatments). Conclusion: Individuals with AD report considerable polypharmacy, which is associated with increased OOP expenses and significant financial impact. Strategies are needed to reduce polypharmacy, minimize OOP costs, and optimize clinical outcomes.

Clinical and economic burden of chronic rhinosinusitis with nasal polyposis: A U.S. administrative claims analysis.

Background: Limited data exist on the clinical and economic burden of chronic rhinosinusitis with nasal polyposis (CRSwNP). Objective: To describe patient characteristics, health-care resource utilization (HCRU), and health-care costs among patients with CRSwNP with and without comorbid asthma (primary analysis) and with surgical management of nasal polyps (secondary analysis). Methods: This was a retrospective study of patients diagnosed with CRSwNP conducted using administrative claims data from January 1, 2013, through March 31, 2019. Study outcomes were assessed over a 2-year follow-up. Results were stratified by baseline asthma status (primary analysis) and presented separately for patients with surgically managed CRSwNP (secondary analysis). Results: The primary analysis included 10,999 patients with CRSwNP (2649 with asthma, 8350 without asthma). Patients with versus without asthma had higher medication use, HCRU, and all-cause medical costs (mean ± standard deviation $34,667 ± $42,234 versus $27,122 ± $45,573; p < 0.001) across the full follow-up period. CRSwNP-related medical costs were significantly higher for patients with versus without asthma in year 2 of follow-up. In the surgical management analysis (n = 4943), most categories of medication use and CRSwNP-related HCRU declined from baseline levels during follow-up, and CRSwNP-related pharmacy costs in year 2 were less than half of baseline levels. Conclusion: Patients diagnosed with CRSwNP and asthma had a greater burden of illness than those without asthma. Higher CRSwNP-related medical costs in year 2 of follow-up for patients with asthma may indicate worsening symptoms over time. Among patients with surgically managed CRSwNP, HCRU and costs increased in year 1 of follow-up but decreased below baseline levels in year 2, potentially reflecting improved symptom severity.

Bayesian Comorbidity Network and Cost Analysis for Asthma.

The evolving disease spectrum poses significant challenges to the asthma management, thus worsening health quality and increased financial burden on patients. However, potential dependency pattern in comorbidity spectrum remains unclear. We built comorbidity networks based on Bayesian networks utilizing 19604 asthma-patient hospitalization data to investigate dependency patterns among asthma comorbidities. We analyze static properties and trajectory behaviors of gender- and age-stratified asthmatic comorbidity networks. Results suggest that chronic obstructive pulmonary disease, respiratory failure, hypertension, atherosclerosis, and gastritis and duodenitis are the hubs of the asthma comorbidity network. They have a strong dependency pattern, while most of the associations among other comorbidities are sparse and weak. The strength of association between comorbidities is higher in female asthmatics than in males. Although the comorbidity network in children with asthma is simple and stable, the onset of common comorbidities as they age will enhance the association between comorbidities and thus increase the risk of developing other comorbidities. Furthermore, the more attributes of comorbidities, the stronger association with each other, and the greater risk of causing high treatment costs. Our study will help to dissect the asthma co-morbidity network and provide a basis for improving asthma management and cost control.

Prevalence, clinical presentation, and associated atopic diseases of pediatric fruit and vegetable allergy: A population-based study.

In children, fruit and vegetable allergies are often overlooked compared with well-known allergies such as those to eggs, milk, and shellfish. Therefore, this study aimed to analyze fruit and vegetable allergies in children, including prevalence, types of food allergens, clinical presentation, management, and associated comorbid atopic diseases. In 2012, a nationwide, cross-sectional, random sampling questionnaire-based survey for common fruit and vegetable allergies was conducted in Taiwan. Information regarding these plant food allergies was collected. Physicians diagnosed food allergies according to the descriptions of convincing symptoms. Enrolled questionnaires were reviewed by expert pediatricians. A total of 9,982 valid questionnaires were analyzed. The overall prevalence of fruit and vegetable allergies was 5.6% (n=560) and 3.0% (n=304), respectively. The most common fruit allergen was mango, followed by kiwifruit, whereas taro and bamboo shoot were the most common vegetable allergens. Meanwhile, most allergic symptoms were of the mucocutaneous tissue, followed by the upper airway and gastrointestinal tract. Most only required avoidance of allergens and not medical treatment. Children with fruit or vegetable allergies had a higher percentage of comorbid atopic dermatitis, allergic rhinitis, and asthma than those without food allergies; additionally, the proportion of comorbid atopic diseases was similar between fruit and vegetable allergies and shellfish allergy. One child developed anaphylaxis due to a corn allergy. Fruits and vegetables are common food allergens in Taiwanese children who present with diverse and potentially severe symptoms. Children with plant food allergies had a percentage of comorbid atopic diseases similar to that of shellfish allergy, the most common allergen. These findings indicate the importance of considering fruit and vegetable allergies in children.

Prevalence of adult self-reported atopic dermatitis in Greece: results from a nationwide survey

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder. In Greece, there is a lack of data on AD epidemiology. The objective of the present study was to estimate the self-reported prevalence of AD and the prevalence of moderate/severe AD in the adult population in Greece. A nationwide cross-sectional survey with a structured questionnaire was conducted, between June 17th, 2021 and July 12th, 2021, using Computer Assisted Telephone Interviewing (CATI) and Computer Assisted web Interviewing (CAWI) data collection methods. Several different self-reported AD definitions, as extracted from the literature, were used. Self-reported moderate/severe atopic dermatitis was estimated using the Patient Oriented Eczema Measure (POEM). More than 30,500 persons were invited to participate; among them, 3,001 were recruited for the survey. The 12-month self-reported AD prevalence in Greece ranged from 1.7% to 6.4%, while lifetime prevalence reached 11.4%. At least half of the responders who identified with AD during the last 12 months had moderate to very severe eczema. The multivariate analysis confirmed that age, atopy-related comorbidities (asthma, allergies, and rhinitis), a family history of AD, rhinitis, and asthma were factors that are independently associated with AD, irrespective of the definition used. The 12-month and lifetime prevalence of AD in adults in Greece ranges from 1.7% to 6.4% and 3.7% to 11.4%, respectively. At least half of the adults with AD suffer from moderate-to-severe disease. Our study is a first step in understanding AD epidemiology in Greece and may provide useful insights for healthcare decision makers.

Systemic Corticosteroid–related Adverse Outcomes and Health Care Resource Utilization and Costs Among Patients with Chronic Rhinosinusitis with Nasal Polyposis

PurposeNasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure. MethodsThis retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBMⓇ MarketScanⓇ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1–3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period. FindingsSCS users (n = 37,740) had a greater risk for any adverse outcome than controls (n = 7032) (incidence rate ratio [IRR] = 1.10; 95% CI, 1.05–1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (n = 2993) versus controls who did not have NP surgery (n = 5078) (IRR = 1.30; 95% CI, 1.18–1.44). Similarly, patients with asthma and ≥4 SCS claims (n = 4195) had a greater risk for SCS-related outcomes versus controls with asthma (n = 1226) (IRR = 1.36; 95% CI, 1.19–1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001). ImplicationsIn patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP.

Prediction of Asthma Risk Using Family Health Histories identified from Population-based Electronic Healthcare Records.

ObjectivesPrediction of asthma risk can potentially be improved by including family history of asthma and related diagnoses, which reflect both genetics and shared environments. We tested the improvements in offspring asthma risk prediction using objectively-measured maternal, paternal, and offspring histories of comorbid conditions from administrative healthcare databases. ApproachA population-based cohort study was conducted using data from Manitoba, Canada. Children born from 1974 to 2000 with linkages to at least one parent using family identification numbers were included. Asthma diagnosis and comorbidities were identified from hospital and outpatient physician visit records. Lasso regression models were used to assess performance and identify important predictors. The base model included offspring demographics, diagnosed allergic conditions and respiratory infections, and diagnosed parental asthma. Subsequent models included multiple comorbid chronic health conditions for offspring and parents. ResultsThe cohort included 195,666 offspring; 51% were males, 13.6% had a parental asthma diagnosis, and 17.7% had an asthma diagnosis (median age at diagnosis: 6.0 years; interquartile range 3.0-11.0 years). The base model achieved a modest prediction performance with an area under the receiver operating characteristic curve of 0.60, sensitivity of 0.46 and a specificity of 0.67 using a threshold of 0.20. Sensitivity significantly improved when we included offspring chronic health conditions (sensitivity= 0.69; specificity = 0.66); both measures further improved when we additionally included parents’ chronic health conditions (sensitivity= 0.72; specificity = 0.70). Chronic obstructive pulmonary disease, noninfectious gastroenteritis and otitis media were among the variables that added incremental predictive value of asthma risk with odd ratios of 1.36, 1.25 and 1.18, respectively. ConclusionsIncluding offspring and parents’ chronic health conditions, identified objectively from administrative healthcare databases, improved the performance of asthma risk prediction models in children. Health histories of comorbid conditions provide important factors to improve risk prediction models of chronic health conditions, which will facilitate disease prevention and treatment strategies.

Identification of key genes and pathways in chronic rhinosinusitis with nasal polyps and asthma comorbidity using bioinformatics approaches.

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma comorbidity (ACRSwNP) present severe symptoms and are more likely to relapse. However, the pathogenesis of ACRSwNP is not fully understood. The aim of this study was to explore the underlying pathogenesis of ACRSwNP using bioinformatics approaches. ACRSwNP-related differentially expressed genes (DEGs) were identified by the analysis of the GSE23552 dataset. The clusterProfiler R package was used to carry out functional and pathway enrichment analysis. A protein–protein interaction (PPI) network was built using the STRING database to explore key genes in the pathogenesis of ACRSwNP. The bioinformatics analysis results were verified through qRT-PCR. The Connectivity Map (CMap) database was used to predict potential drugs for the treatment of ACRSwNP. A total of 36 DEGs were identified, which were mainly enriched in terms of regulation of immune response and detection sensory perception of taste. Thirteen hub genes including AZGP1, AQP9, GAPT, PIP, and PRR4 were identified as potential hub genes in ACRSwNP from the PPI network. Analysis of the GSE41861 dataset showed that upregulation of CST1 in nasal mucosa was associated with asthma. qRT-PCR detection confirmed the bioinformatics analysis results. Tacrolimus and spaglumic acid were identified as potential drugs for the treatment of ACRSwNP from the CMap database. The findings of this study provide insights into the pathogenesis of ACRSwNP and may provide a basis for the discovery of effective therapeutic modalities for ACRSwNP.

Asthma and asthma-related comorbidity: effects on nocturnal oxygen saturation.

Nocturnal symptoms are very common in asthma, which is associated with worse sleep quality. The nocturnal oxygen saturation may be decreased in asthma; however, whether this association is dependent on nocturnal asthma symptoms, lung function, coexisting obstructive sleep apnea (OSA), or other asthma-related comorbidities is unknown. The objective of this study was to examine the effects of asthma, OSA, lung function, airway symptoms, and asthma-related comorbidities on the nocturnal oxygen saturation in a cross-sectional community-based population study. In total, 395 women and 392 men underwent overnight polysomnography, performed spirometry, and completed questionnaires on airway symptoms and asthma-related comorbidities. Participants with asthma (n = 88) had a lower nocturnal oxygen saturation than those without asthma (93.8% vs 94.3%, P = .01) also after adjusting for comorbidity, age, body mass index, and smoking status (coefficient -0.38; CI -0.67, -0.10; P < .01). The nocturnal oxygen saturation was lower among participants with wheezing, nocturnal chest tightness, fixed airflow limitation, gastroesophageal reflux, obesity, and OSA than in those without these conditions. The associations between lower oxygen saturation and wheezing, forced expiratory volume in 1 second, gastroesophageal reflux, and apnea-hypopnea index were significant also after adjusting for age, sex, body mass index, and smoking status. Participants with both wheezing and OSA had a significantly lower nocturnal oxygen saturation (92.5 ± 0.5%) than participants with wheezing only (94.3 ± 0.3%) and OSA only (93.6 ± 0.2% %) (P < .01). Participants with asthma displayed a lower mean oxygen saturation during sleep, which could not be explained only by coexisting OSA or obesity. Also, asthma symptoms and lung function were associated with lower nocturnal oxygen saturation. The lower oxygen saturation seen in asthma is hence multifactorial in origin and is a result of the combination of symptoms, lung function, and comorbidity. Sundbom F, Janson C, Ljunggren M, Lindberg E. Asthma and asthma-related comorbidity: effects on nocturnal oxygen saturation. J Clin Sleep Med. 2022;18(11):2635-2641.

Survival, mortality, and related comorbidities among COVID-19 patients in Saudi Arabia: A hospital-based retrospective cohort study.

To assess the survival of COVID-19 patients in Saudi Arabia and to investigate possible mortality predictors. This is a retrospective cohort study involving 248 patients with severe acute respiratory syndrome coronavirus-2 who were admitted to the primary COVID-19 referral hospital in Jeddah between March and June of 2020. Socio-demographic characteristics, comorbidities, laboratory investigations, management protocols, complications, treatment options, and mortality data were extracted from electronic medical records. The time analysis began at the first signs of illness thorough discharge or death. Our study showed that in-hospital complications including heart failure followed by acute renal failure had the largest effect size on mortality (p<0.001). Elderly patients and those with comorbid asthma had a higher risk of death. Non-survivors presented more commonly with shortness of breath and fever than survivors. High D-Dimer level was a marginally significant indicator of mortality in the studied population (p=0.05). We did not find a significant benefit in relation to any treatment option. Age, asthma, some in-hospital complications are important survival indicators in hospitalized COVID-19 patients. The controllable co-factors should be monitored and managed by healthcare workers to reduce mortality rates in those hospitalized with COVID-19.