The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation.

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

Retrospective review of acute post-tracheostomy complications and contributing risk factors.

OBJECTIVE: Tracheostomy is performed for various indications ranging from prolonged ventilation to airway obstruction. Many factors may play a role in the incidence of complications in the immediate post-operative period including patient-related factors. Chronic obstructive pulmonary disease and asthma are some of the most common pulmonary pathologies in the United States. The relationship between obstructive pulmonary diseases and acute post-tracheostomy complications has been incompletely studied. DESIGN: A retrospective chart review was designed in order to answer these objectives. Medical records were reviewed for the technique used, complications, and contributing patient factors. Post-operative complications were defined as any tracheostomy-related adverse event occurring within 14 days. SETTING: The study took place at an academic comprehensive cancer. PARTICIPANTS: Inclusion criteria included patients from January 2017 through December 2018 who underwent a tracheostomy. Exclusion criteria included presence of stomaplasty, total laryngectomy, and tracheostomies performed at outside hospitals. MAIN OUTCOME MEASURES: Patient factors examined included demographics, comorbidities, and body mass index with the primary outcome measured being the rate of tracheostomy complications. RESULTS: The most common indication for tracheostomy among the 321 patients that met inclusion criteria was airway obstruction or a head and neck cancer surgical procedure. Obstructive sleep apnea was associated with acute complications in bivariate analysis (29.4% complications, p = .003). Chronic obstructive pulmonary disease and asthma were not associated with acute complications in bivariate analysis (11.6% complications, p = .302). Among the secondary outcomes measured, radiation was associated with early complications occurring in post-operative days 0-6 (1.1%, p = .029). CONCLUSION: Patients with obstructive sleep apnea may have a higher risk of acute post-tracheostomy complications that might be due to the patient population at risk for obstructive sleep apnea. Patients with obstructive pulmonary pathologies such as asthma or chronic obstructive pulmonary disorder did not have an elevated risk of complications which is clinically significant when considering the utility of ventilation and tracheostomy in the management of acute respiratory failure secondary to these conditions.

The therapeutic role of inspiratory muscle training in the management of asthma: a narrative review.

Asthma is a disorder of the airways characterized by chronic airway inflammation, hyperresponsiveness, and variable recurring airway obstruction. Treatment options for asthma include pharmacological strategies, whereas nonpharmacological strategies are limited. Established pharmacological approaches to treating asthma may cause unwanted side effects and do not always afford adequate protection against asthma, possibly because of an individual's variable response to medications. A potential nonpharmacological intervention that is most available and cost effective is inspiratory muscle training (IMT), which is a technique targeted at increasing the strength and endurance of the diaphragm and accessory muscles of inspiration. Studies examining the impact of IMT on asthma have reported increases in inspiratory muscle strength and a reduction in the perception of dyspnea and medication use. However, because of the limited number of studies and discordant methods between studies more evidence is required to elucidate in individuals with asthma the efficacy of IMT on inspiratory muscle endurance, exercise capacity, asthma control, symptoms, and quality of life as well as in adolescents with differing severities of asthma. Large randomized controlled trials would be a significant step forward in clarifying the effectiveness of IMT in individuals with asthma. Although IMT may have favorable effects on inspiratory muscle strength, dyspnea, and medication use, the current evidence that IMT is an effective treatment for asthma is inconclusive.

Asthma as an Inflammatory Reason of Tracheobronchial PSMA Uptake.

ABSTRACT: A 53-year-old man with persisting increased serum prostate-specific antigen level (9.53 ng/mL) and repeated negative prostate biopsies was referred for a PET/CT with 68 Ga-PSMA-11. The PET/CT revealed focal uptake in the prostate suggestive of localized prostate cancer. Incidentally, it also showed a diffuse uptake in the tracheobronchial tree suspicious for a benign etiology. Because of the clinical history of asthma exacerbation in the previous week, further supplementary studies were performed showing a pathological fractional exhaled nitric oxide level (92 ppb; reference values, <25 ppb) and mild airway obstruction in the spirometry. These findings confirmed asthma as an inflammatory etiology of the tracheobronchial PSMA uptake.

Case Report: Antifungal Agents in the Treatment of Asthma and Allergy After Water-Damaged Building Exposure.

Damp and moisture-damaged building exposure has been linked to adverse health effects, primarily related to respiratory complications from mold spore reactions. This paper describes a case of a previously healthy man who was exposed to a home with hidden mold infestation and remained symptomatic following proper remediation. The patient presented with allergies, allergic bronchopulmonary aspergillosis, and treatment resistant asthma, as well as other non-respiratory symptoms likely related to inhalational mycotoxin exposure from his home. In this case, the addition of systemic and intranasal antifungals improved both respiratory and non-respiratory symptoms. Antifungals were used for a longer duration than customary and in combination with factors that addressed drug resistance.

Effect of long-term medium to high-dose inhaled budesonide on bone mineral density in children with asthma: a cross-sectional study.

OBJECTIVE: The objective of this study was to examine the impact of long-term medium to high-dose inhaled budesonide on bone mineral density in children with asthma. METHODS: We conducted a cross-sectional study in children aged 7-17 years with asthma, who received long-term (≥2 years), medium to high-dose inhaled budesonide (≥400µg/day in 6-11 years old; ≥800 µg/day in >11 years old). We measured bone mineral density (BMD) using dual-energy X-ray absorptiometry and compared it with reference Indian normative values. RESULTS: Thirty-five children with moderate to severe asthma receiving long-term medium to high-dose inhaled budesonide, were included in the study. We found a significantly low lumbar-spine BMD in the study population compared to reference Indian values (p-value 0.002). Eight cases had short stature. Despite the adjustment for height-age in these short-stature cases, lumbar-spine BMD remained significantly low in the study population (p-value 0.020). No significant difference was found in 25-hydroxy vitamin D levels between subjects with "low BMD" and "BMD z-score > -2". CONCLUSIONS: The findings of this study suggest that long-term medium to high-dose inhaled budesonide treatment in children with asthma is associated with decreased BMD. However, further investigation with a larger sample size is necessary to confirm this relationship.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

OBJECTIVE: To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. INTERVENTION: Treatment with targeted biologic therapy. MAIN OUTCOME MEASURES: Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. RESULTS: Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). CONCLUSIONS: Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. LEARNING OBJECTIVE: To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. DESIRED RESULT: Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. LEVEL OF EVIDENCE: Level IV. INDICATE IRB OR IACUC: Exempt. HUM00182703.

Biofeedback Training to Increase P co2 in Asthma With Elevated Anxiety: A One-Stop Treatment of Both Conditions?

OBJECTIVE: Anxiety is highly prevalent in individuals with asthma. Asthma symptoms and medication can exacerbate anxiety, and vice versa. Unfortunately, treatments of comorbid anxiety and asthma are largely lacking. A problematic feature common to both conditions is hyperventilation. It adversely affects lung function and symptoms in asthma and anxiety. We examined whether a treatment to reduce hyperventilation, shown to improve asthma symptoms, also improves anxiety in asthma patients with high anxiety. METHOD: One hundred twenty English- or Spanish-speaking adult patients with asthma were randomly assigned to either Capnometry-Assisted Respiratory Training (CART) to raise P co2 or feedback to slow respiratory rate (SLOW). Although anxiety was not an inclusion criterion, 21.7% met clinically relevant anxiety levels on the Hospital Anxiety and Depression Scale (HADS). Anxiety (HADS-A) and depression (HADS-D) scales, anxiety sensitivity (Anxiety Sensitivity Index [ASI]), and negative affect (Negative Affect Scale of the Positive Affect Negative Affect Schedule) were assessed at baseline, posttreatment, 1-month follow-up, and 6-month follow-up. RESULTS: In this secondary analysis, asthma patients with high baseline anxiety showed greater reductions in ASI and PANAS-N in CART than in SLOW ( p values ≤ .005, Cohen d values ≥ 0.58). Furthermore, at 6-month follow-up, these patients also had lower ASI, PANAS-N, and HADS-D in CART than in SLOW ( p values ≤ .012, Cohen d values ≥ 0.54). Patients with low baseline anxiety did not have differential outcomes in CART than in SLOW. CONCLUSIONS: For asthma patients with high anxiety, our brief training designed to raise P co2 resulted in significant and sustained reductions in anxiety sensitivity and negative affect compared with slow-breathing training. The findings lend support for P co2 as a potential physiological target for anxiety reduction in asthma. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00975273 .

The Role of Lung Function in Determining Which Children Develop Asthma.

Longitudinal studies have demonstrated that altered indices of airway function, assessed shortly after birth, are a risk factor for the subsequent development of wheezing illnesses and asthma, and that these indices predict airway size and airway wall thickness in adult life. Pre- and postnatal factors that directly alter early airway function, such as extreme prematurity and cigarette smoke, may continue to affect airway function and, hence, the risks for wheeze and asthma. Early airway function and an associated asthma risk may also be indirectly influenced by immune system responses, respiratory viruses, the airway microbiome, genetics, and epigenetics, especially if they affect airway epithelial dysfunction. Few if any interventions, apart from smoking avoidance, have been proven to alter the risks of developing asthma, but vitamin C supplementation to pregnant smokers may help decrease the effects of in utero smoke on offspring lung function. We conclude that airway size and the factors influencing this play an important role in determining the risk for asthma across the lifetime. Progress in asthma prevention is long overdue and this may benefit from carefully designed interventions in well-phenotyped longitudinal birth cohorts with early airway function assessments monitored through to adulthood.

Prepregnancy body mass index and risk of childhood asthma.

BACKGROUND: Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child's risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk. METHODS: Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005-2014) to age 4 (n = 104,467), 6 (n = 63,084), or 8 (n = 31,006) using electronic medical records. Child's asthma was defined using ICD codes and asthma-related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child's asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese 1 [30-34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI. RESULTS: Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI. CONCLUSIONS: Higher prepregnancy BMI is associated with modestly increased childhood asthma risk.

Do Biologic Therapies Decrease Mucus Plugging in Asthma?

Asthma researchers have long recognized that abnormal mucus production and clearance play a role in the pathophysiology of asthma.1 Mucus plugs are known to be common in patients with severe asthma, and mucus plug scores, for which higher scores indicate more severe plugging, are directly correlated with airflow obstruction and markers of eosinophilic airway inflammation (i.e., higher scores or marker levels are associated with more severe obstruction). Other work has shown that mucus plugs were associated with distal deficits in regional ventilation as delineated by hyperpolarized gas magnetic resonance imaging.2,3.

A randomized, double-blind, placebo-controlled multicenter clinical trial of Xiehuang Jiejing granule in the treatment of cough variant asthma in children.

BACKGROUND: Cough variant asthma (CVA), also called concealed asthma or allergic asthma, is the most common cause of chronic cough in children. The disorder is mainly characterized by a nonproductive dry cough associated with a high recurrence rate that is conventionally treated with antibiotics, anti-inflammatory medications, cough suppressants, or expectorants. For millennia, Chinese herbal medicine (CHM) has been used widely in China to treat pediatric CVA cases, although high-quality evidence of CHM efficacy is lacking. In this study, the effectiveness and safety of Xiehuangjiejing (XHJJ) granule will be evaluated when used alone to treat children with CVA. METHODS AND ANALYSIS: A randomized, double-blind, parallel, placebo-controlled multicenter trial will be conducted over the course of 2 weeks. A total of 180 CVA patients of ages between 4 and 7 years old will be randomly assigned to the experimental group (XHJJ granules, 4.5 g administered 3 times daily) or control group (matched placebo, 4.5 g administered 3 times daily) in a 2:1 ratio based on subject number per group, respectively. The trial will consist of a 7-day medical interventional stage and a 7-day follow-up stage. On day 7 of the follow-up stage, an evaluation of all subjects will be carried out to assess cough symptom score as the primary outcome and several secondary outcomes, including TCM (traditional Chinese medicine) syndrome score, lung function, and dosage of salbutamol aerosol inhaler therapy. Safety assessments will also be evaluated during the trial. DISCUSSION: The aim of this study was to examine the effectiveness and safety of Xiehuangjiejing (XHJJ) granule using a trial protocol designed to yield high-quality, statistically robust results for use in evaluating CHM as a treatment for CVA in children.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Atopic heredity modifies the association between maternal vitamin D status in pregnancy and the risk of atopic disease in childhood: an observational study.

BACKGROUND: The relationship between maternal vitamin D status in pregnancy and the development of atopic diseases in the offspring has been frequently studied, but with contradictory results. Previous studies have found an inverse relation between maternal vitamin D in pregnancy and the risk of atopic diseases in the child. In contrast, others have found a higher maternal 25OHD to be related to a higher risk of atopic diseases. Thus, the aim was to investigate the associations between maternal vitamin D status and intake in pregnancy with asthma, eczema and food allergies in the children up to 5 years. In addition, effect modification by reported atopic heredity was studied. METHODS: Participants in the GraviD study had 25-hydroxyvitamin D (25OHD) analyzed in serum in early (T1) and late (T3) pregnancy. Maternal dietary vitamin D intake was estimated from a short food frequency questionnaire and supplement use by questionnaires. At 5 years of age the child´s history of asthma, eczema and food allergy, including atopic heredity, was reported by questionnaire. Multivariable logistic regression was used. RESULTS: The cumulative incidence of asthma was 13%, eczema 22%, and food allergy 18%. Only among children without reported atopic heredity, maternal 25OHD of 50-75 nmol/L in T1 was associated with lower odds of asthma (OR 0.271, 95% CI 0.127-0.580), compared to maternal 25OHD > 75 nmol/L. Additionally in these children, maternal 25OHD in T3 (continuous) was associated with asthma (OR 1.014, 95% CI 1.002-1.009), and dietary vitamin D intake with eczema (OR 1.141, 95% CI 1.011-1.288). CONCLUSIONS: Among children without reported atopic heredity, higher maternal vitamin D status and intake during pregnancy was associated with increased risk of reported atopic disease.

Comparison of the risks of occupational diseases, avoidable hospitalization, and all-cause deaths between firefighters and non-firefighters: A cohort study using national health insurance claims data.

Objectives: National Health Insurance claims data were used to compare the incidence of occupational diseases, avoidable hospitalization, and all-cause death standardized incidence ratio and hazard ratio between firefighters and non-firefighters. Methods: The observation period of the study was from 2006 to 2015 and a control group (general workers and national and regional government officers/public educational officers) and a firefighter group was established. The dependent variables were occupational diseases, avoidable hospitalization (AH), and all-cause death. The analysis was conducted in three stages. First, the standardized incidence ratios were calculated using the indirect standardization method to compare the prevalence of the disease between the groups (firefighter and non-firefighter groups). Second, propensity score matching was performed for each disease in the control group. Third, the Cox proportional hazards model was applied by matching the participants. Results: The standardized incidence ratio and Cox regression analyses revealed higher rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, cancer, back pain, admission due to injury, mental illness, depression, and AH for firefighters than general workers. Similarly, the rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, back pain, admission due to injury, mental illness, depression, and AH were higher in the firefighter group than in the national and regional government officer/public educational officer group. Conclusions: The standardized incidence ratios and hazard ratios for most diseases were high for firefighters. Therefore, besides the prevention and management of diseases from a preventive medical perspective, management programs, including social support and social prescriptions in the health aspect, are needed.

Influence of vitamin D supplementation on the quality of life of asthma patients: Findings from ACVID randomised clinical trial.

Published data on vitamin D and the quality of life of asthma patients are scarce and disparate. The ACVID clinical trial, published in 2020, showed the efficacy of calcifediol in improving asthma control in asthma patients with vitamin D deficiency. Data on vitamin D and quality of life measured by the Mini-AQLQ questionnaire were analysed: supplemented patients showed improved quality of life compared with a placebo group, and the initial mini-AQLQ scores were improved for both groups.

Dual biologic therapy in a patient with severe asthma and other allergic disorders.

Severe asthma is very difficult to manage in many individuals, and systemic corticosteroids are often used to prevent or manage acute exacerbations. Furthermore, comorbid allergic conditions may render standard therapies inadequate. A 51-year-old man presented with severe eosinophilic asthma requiring nearly constant oral corticosteroid usage despite using high-dose inhaled corticosteroids and secondary asthma controllers. His condition was complicated by aspirin-exacerbated respiratory disease, including severe nasal polyposis, chronic rhinosinusitis, as well as chronic idiopathic urticaria. Mepolizumab was initiated and led to dramatic improvement of asthma over 6 months. However, he continued to experience exacerbations of chronic idiopathic urticaria not responsive to H1-antihistamines. Omalizumab was added, and the patient's urticaria attained marked improvement with only an occasional breakthrough rash. Dual biologic therapies can be a unique and useful steroid-sparing treatment option for patients with uncontrolled severe asthma and chronic idiopathic urticaria.