Worsening Of Asthma Research Articles

Adverse effects of monoclonal antibodies in the treatment of moderate-to-severe asthma: a narrative review

Introduction and purpose: Over the past two decades, the management of severe asthma shifted from high doses of inhaled and oral corticosteroids to targeted biologic agents. Adverse effects of treatment with monoclonal antibodies are not yet fully characterised. The aim of this paper is to provide a comprehensive review of the adverse effects of the FDA-approved monoclonal antibodies in the treatment of moderate-to-severe asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab. Material and methods of research: A thorough literature review was performed using PubMed Web of Science and Embase, employing key words related to monoclonal antibodies, asthma and adverse effects. Description of the state of knowledge: Omalizumab and mepolizumab have black box warning on the risk of anaphylaxis. Due to scarcity of data, no causal association between the use of monoclonal antibodies and risk of malignancy can be established. The most common adverse effects of biologic agents in severe asthma include upper respiratory tract infections, nasopharyngitis and asthma worsening. Conclusions: Overall, monoclonal antibodies have a favourable safety profile, with certain risk of side effects remains present, and is variable for the different molecules. More studies of asthmatic patients treated with monoclonal antibodies are needed to spot rare adverse events and those developing over longer time.

Neutrophil and neutrophil extracellular trap involvement in neutrophilic asthma: A review.

Asthma is a highly prevalent chronic inflammatory disease characterized by variable airflow obstruction and airway hyperresponsiveness. Neutrophilic asthma (NA) is classified as "type 2 low" asthma, defined as 65% or more neutrophils in the total cell count. There is no clear consensus on the pathogenesis of NA, and the accumulation of neutrophils and release of neutrophil extracellular traps (NETs) may be responsible for its development. A NET is a large extracellular meshwork comprising cell membrane and granule proteins. It is a powerful antimicrobial defence system that traps, neutralizes, and kills bacteria, fungi, viruses, and parasites and prevents the spread of microorganisms. However, dysregulation of NETs may lead to chronic airway inflammation, is associated with worsening of asthma, and has been the subject of major research advances in chronic lung diseases in recent years. NA is insensitive to steroids, and there is a need to find effective biomarkers as targets for the treatment of NA to replace steroids. This review analyses the mechanisms of action between asthmatic neutrophil recruitment and NET formation and their impact on NA development. It also discusses their possible therapeutic significance in NA, summarizing the advances made in NA agents and providing strategies for the treatment of NA, provide a theoretical basis for the development of new therapeutic drugs, thereby improving the level of diagnosis and treatment, and promoting the research progress in the field of asthma.

Comparative safety of monoclonal antibodies in chronic inflammatory airway diseases (chronic sinusitis with nasal polyposis and asthma): A network meta-analysis

ObjectiveSeveral monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA). MethodsElectronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs’ safety data. Results1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased. ConclusionOverall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs.Trial Registration: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).

Pharmacists’ clinical decision making when responding to a self-medication request for a cough in a developing country

BackgroundSome studies have reported that community pharmacies in developing countries, including Indonesia, provided sub-optimal advice when handling patient's self-medication request for cough. The reasons behind such advice, therefore, need to be investigated. ObjectivesTo describe Indonesian pharmacists’ clinical decision making when handling self-medication cases for a cough. MethodsAn open-ended questionnaire consisting of two cough clinical vignettes (case 1: cough due to asthma worsening and case 2: cough as a symptom of common cold) were developed. Pharmacists were interviewed to provide recommendations and reasons for their recommendations for these scenarios. Content analysis was used to analyse participants’ statements for the two scenarios. The number of participants who provided appropriate recommendations and reasons were then counted. ResultsA total of 245 community pharmacists participated in the study. In the case of cough due to asthma worsening, recommending a product because the product was indicated to help with the symptoms was the most common recommendation and stated reason (40%). Appropriate recommendation (direct medical referral) with appropriate reasoning (indicating warning symptoms and/or making a symptom diagnosis) was provided by 25% participants. In the case of cough as a symptom of common cold, recommending products to help with the symptoms was also the most common recommendation and stated reason (53%). Appropriate recommendations (recommending product) with appropriate reasoning (providing product to treat the symptoms and/or indicating no warning symptoms and/or making a symptom diagnosis) was provided by 81% participants. ConclusionThe ability of Indonesian community pharmacists to provide appropriate recommendations for cough self-medication requests is dependent on whether triage is required. The inability of most community pharmacists to differentiate between major and minor conditions may lead to serious health implications for patients and therefore educational interventions should be undertaken to improve community pharmacists’ differential diagnostic skills for triage.

Digital Self-Management Platform for Adult Asthma: Randomized Attention-Placebo Controlled Trial.

Asthma is one of the most common chronic conditions worldwide, with a substantial individual and health care burden. Digital apps hold promise as a highly accessible, low-cost method of enhancing self-management in asthma, which is critical to effective asthma control. We conducted a fully remote randomized controlled trial (RCT) to assess the efficacy of juli, a commercially available smartphone self-management platform for asthma. We conducted a pragmatic single-blind, RCT of juli for asthma management. Our study included participants aged 18 years and older who self-identified as having asthma and had an Asthma Control Test (ACT) score of 19 or lower (indicating uncontrolled asthma) at the beginning of the trial. Participants were randomized (1:1 ratio) to receive juli for 8 weeks or a limited attention-placebo control version of the app. The primary outcome measure was the difference in ACT scores after 8 weeks. Secondary outcomes included remission (ACT score greater than 19), minimal clinically important difference (an improvement of 3 or more points on the ACT), worsening of asthma, and health-related quality of life. The primary analysis included participants using the app for 8 weeks (per-protocol analysis), and the secondary analysis used a modified intention-to-treat (ITT) analysis. We randomized 411 participants between May 2021 and April 2023: a total of 152 (37%) participants engaged with the app for 8 weeks and were included in the per-protocol analysis, and 262 (63.7%) participants completed the week-2 outcome assessment and were included in the modified ITT analysis. Total attrition between baseline and week 8 was 259 (63%) individuals. In the per-protocol analysis, the intervention group had a higher mean ACT score (17.93, SD 4.72) than the control group (16.24, SD 5.78) by week 8 (baseline adjusted coefficient 1.91, 95% CI 0.31-3.51; P=.02). Participants using juli had greater odds of achieving or exceeding the minimal clinically important difference at 8 weeks (adjusted odds ratio 2.38, 95% CI 1.20-4.70; P=.01). There were no between group differences in the other secondary outcomes at 8 weeks. The results from the modified ITT analyses were similar. Users of juli had improved asthma symptom control over 8 weeks compared with users of a version of the app with limited functionality. These findings suggest that juli is an effective digital self-management platform that could augment existing care pathways for asthma. The retention of patients in RCTs and real-world use of digital health care apps is a major challenge. International Standard Randomised Controlled Trial Number (ISRCTN) registry ISRCTN87679686; https://www.isrctn.com/ISRCTN87679686.

Impact of liquid sublingual immunotherapy on asthma onset and progression in patients with allergic rhinitis: a nationwide population-based study (EfficAPSI study)

BackgroundThe only disease-modifying treatment currently available for allergic rhinitis (AR) is allergen immunotherapy (AIT). The main objective of the EfficAPSI real-world study (RWS) was to evaluate the impact of liquid sublingual immunotherapy (SLIT-liquid) on asthma onset and evolution in AR patients. MethodsAn analysis with propensity score weighting was performed using the EfficAPSI cohort, comparing patients dispensed SLIT-liquid with patients dispensed AR symptomatic medication with no history of AIT (controls). Index date corresponded to the first dispensation of either treatment. The sensitive definition of asthma event considered the first asthma drug dispensation, hospitalisation or long-term disease (LTD) for asthma, the specific one omitted drug dispensation and the combined one considered omalizumab or three ICS+/-LABA dispensation, hospitalisation or LTD. In patients with pre-existing asthma, the GINA treatment step-up evolution was analysed. FindingsIn this cohort including 112 492 SLIT-liquid and 333 082 controls, SLIT-liquid exposure was associated with a significant lower risk of asthma onset versus control, according to all definitions (combined: HR [95%CI]=0·62 [0·60-0·63], sensitive: 0·77 [0·76-0·78], and specific: 0·67 [0·61-0·72]). Exposure to SLIT was associated with a one-third reduction in GINA step-up regardless baseline steps. InterpretationIn this national RWS with the largest number of person-years of follow-up to date in the field of AIT, SLIT-liquid was associated with a significant reduction in the risk of asthma onset or worsening. The use of three definitions (sensitive or specific) and GINA step-up reinforced the rigorous methodology, substantiating SLIT-liquid evidence as a causal treatment option for patients with respiratory allergies. FundingStallergenes Greer

Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses.

Perimenstrual worsening of asthma occurs in up to 40% of women with asthma, leading to increased acute exacerbations requiring clinical care. The role of sex hormones during these times remains unclear. In the current study, we used a translational approach to determine whether progesterone exacerbates allergic inflammation in the traditional chicken egg ovalbumin (OVA) model in BALB/c mice. Simultaneously, we used peripheral blood mononuclear cells (PBMC) from healthy human donors to assess the effects of progesterone on circulating group 2 innate lymphoid cells (ILC2). Briefly, lungs of ovariectomized (OVX) or sham-operated female (F-Sham) controls were implanted with a progesterone (P4, 25 mg) (OVX-P4) or placebo pellet (OVX-Placebo), followed by sensitization and challenge with ovalbumin (OVA). Progesterone increased total inflammatory histologic scores, increased hyper-responsiveness to methacholine (MCh), increased select chemokines in the bronchoalveolar lavage (BAL) and serum, and increased ILC2 and neutrophil numbers, along the airways compared with F-Sham-OVA and OVX-Placebo-OVA animals. Lung ILC2 were sorted from F-Sham-OVA, OVX-Placebo-OVA and OVX-P4-OVA treated animals and stimulated with IL-33. OVX-P4-OVA lung ILC2 were more responsive to interleukin 33 (IL-33) compared with F-Sham-OVA treated, producing more IL-13 and chemokines following IL-33 stimulation. We confirmed the expression of the progesterone receptor (PR) on human ILC2, and showed that P4 + IL-33 stimulation also increased IL-13 and chemokine production from human ILC2. We establish that murine ILC2 are capable of responding to P4 and thereby contribute to allergic inflammation in the lung. We confirmed that human ILC2 are also hyper-responsive to P4 and IL-33 and likely contribute to airway exacerbations following allergen exposures in asthmatic women with increased symptoms around the time of menstruation.NEW & NOTEWORTHY There is a strong association between female biological sex and severe asthma. We investigated the allergic immune response, lung pathology, and airway mechanics in the well-described chicken egg ovalbumin (OVA) model with steady levels of progesterone delivered throughout the treatment period. We found that progesterone enhances the activation of mouse group 2 innate lymphoid cells (ILC2). Human ILC2 are also hyper-responsive to progesterone and interleukin 33 (IL-33), and likely contribute to airway exacerbations following allergen exposures in women with asthma.

A pilot study to assess the effects of preventing fluid retention in the legs by wearing compression stockings on overnight airway narrowing in mild asthma.

Nocturnal asthma is a sign of asthma worsening and could be partially due to more fluid drawn into the thorax during sleep by gravitational force and/or pharyngeal collapse in those with obstructive sleep apnea. Wearing compression stockings during the day reduces fluid shift from the legs to the neck overnight. However, the potential effect of wearing compression stockings to reduce fluid accumulation in the leg and to improve nocturnal small airway narrowing in patients with asthma has not been investigated. This study investigates whether reducing leg fluid volume by wearing compression stockings during the day would attenuate small airway narrowing in patients with asthma before and after sleep. We enrolled 11 participants with asthma. All participants underwent overnight polysomnography with or without wearing compression stockings for 2weeks. Before and after sleep, leg fluid volume (LFV) was measured by bioelectrical impedance, and airway narrowing was primarily assessed by respiratory system resistance and reactance at 5Hz (R5 and X5 respectively) using oscillometry. After 2weeks of wearing compression stockings, the LFV measured in the evening was reduced (∆ = - 192.6 ± 248.3ml, p = 0.02), and R5 and X5 improved (∆ = - 0.7 ± 0.9 cmH2O/L/s, p = 0.03 and 0.2 ± 1.4 cmH2O/L/s, p = 0.05 respectively). No changes were observed in the morning. Preventing fluid retention in the legs by wearing compression stockings for 2weeks during the day, reduced LFV and airway narrowing in the evening in all participants with asthma, but not in the morning after sleep.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3months (T1), at 6months (T2), at 12months (T3) and finally at 18months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

Oscillometry in Asthma: Respiratory Modeling and Analysis in Occupational and Work-Exacerbated Phenotypes.

Asthma onset or worsening of the disease in adulthood may be associated with occupational asthma (OA) or work-exacerbated asthma (WEA). Oscillometry and respiratory modeling offer insight into the pathophysiology and contribute to the early diagnosis of respiratory abnormalities. This study aims to compare the changes due to OA and WEA and evaluate the diagnostic accuracy of this method. Ninety-nine volunteers were evaluated: 33 in the control group, 33 in the OA group, and 33 in the WEA group. The area under the receiver operator characteristic curve (AUC) was used to describe diagnostic accuracy. Oscillometric analysis showed increased resistance at 4hz (R4, p<0.001), 20hz (R20, p<0.05), R4-R20 (p<0.0001), and respiratory work (p<0.001). Similar analysis showed reductions in dynamic compliance (p<0.001) and ventilation homogeneity, as evaluated by resonance frequency (Fr, p<0.0001) and reactance area (p<0.0001). Respiratory modeling showed increased peripheral resistance (p<0.0001), hysteresivity (p<0.0001), and damping (p<0.0001). No significant changes were observed comparing OA with WEA in any parameter. For OA, the diagnostic accuracy analyses showed Fr as the most accurate among oscillometric parameters (AUC=0.938), while the most accurate from respiratory modeling was hysteresivity (AUC=0.991). A similar analysis for WEA also showed that Fr was the most accurate among traditional parameters (AUC=0.972), and hysteresivity was the most accurate from modeling (AUC=0.987). The evaluation of differential diagnosis showed low accuracy. Oscillometry and modeling have advanced our understanding of respiratory abnormalities in OA and WEA. Furthermore, our study presents evidence suggesting that these models could aid in the early diagnosis of these diseases. Respiratory oscillometry examinations necessitate only tidal breathing and are straightforward to conduct. Collectively, these practical considerations, coupled with the findings of our study, indicate that respiratory oscillometry in conjunction with respiratory modeling, may enhance lung function assessments in OA and WEA.

Alérgenos e Asma Ocupacional na Panificação: uma Revisão da Literatura

Introduction/ framework/ objectives “Baker’s Asthma” is a common type of occupational asthma in the bakery industry, related to the inhalation of allergens present in the work environment. It is a disease that produces high rates of absenteeism and temporary unfit for duty (sick leave). This study aimed to gather information about the presence of allergens present in the bakery sector that can develop occupational asthma, with the aim of potenciate the intervention by occupational health services. Methodology A literature review was carried out, including studies found in the online databases SciELO.Org, RCAAP, CINAHL, MEDLINE and MedicLatina, with research carried out between January and March 2022, with the keywords “Baker”, “Occupational Asthma” and “Allergens”. Full text articles published in the last five years, in English, Portuguese or Spanish, were defined as inclusion criteria. The protocol issue of this review is: “What are the allergens likely to trigger occupational asthma in the bakery area, as well as the preventive behaviors to be adopted?”. Results Baker’s asthma is one of the most common types of occupational asthma associated to exposure to flour dust and the allergens contained in it. Persistent exposure to airborne allergens may result in the initiation or worsening of asthma, as well as ocular and/or nasal symptoms. There is a strong relationship between occupational asthma and workers exposed to cereal flour dust, as well as some behaviors adopted by bakery workers as risk factors. The main allergens are those present in the dust of wheat, rye, barley, corn, oat and soy flours, as well as eggs, milk, buckwheat, sesame seeds, nuts and yeasts present in yeast as enhancers of the development of occupational asthma in the bakery sector. Conclusions The review of allergens and occupational asthma is important for the health of workers who continually inhale flour dust. It is important to identify the allergens that cause baker’s asthma, as it can help to improve the diagnosis and treatments of this disease and prevention programs. Workplace interventions, through the introduction of preventive measures (including individual and collective protection), health education and adequate training of workers, aimed at reducing exposure to allergens, contribute to reduce the incidence of occupational asthma. KEY-WORDS: Occupational Asthma, Allergens, Baker, Occupational Nursing, Occupational Medicine, Occupational Health.

Mitigation potential of local traffic interventions on paediatric asthma incidence in EU cities

Abstract Issue/Problem Motorised road traffic is a major contributor to Nitrogen Dioxide (NO2) emissions, contributing to the development and worsening of asthma. With a substantial and escalating prevalence of asthma in urban areas worldwide, this is an issue of public health significance. Description of the problem Deploying methods such as Random Forests and Boosted Regression Trees, this study aims to determine the potential reduction in paediatric asthma incidence in European cities that could be achieved through policy interventions targeting local traffic reductions, such as car-free days. Results In trafficked areas in European cities such as Brussels and Paris, up to 40% of asthma incidence can be attributed to NO2 exposure. Preliminary results show a potential reduction of 29% [95% CI: 20-34%], 21% [95% CI: 13-25%], and 12% [95% CI: 7-15 %] in paediatric asthma incidence in trafficked areas, central urban areas, and residential areas in Brussels, respectively. In Trafficked and Urban Background Areas in Paris, we found a potential reduction of 17% [95% CI: 11 -19%] and 13% [95% CI: 8-16%] in paediatric asthma incidence respectively. Trends and findings are consistent with several methodologies applied. Lessons Using real-world interventions such as car-free days is an innovative way to assess the mitigation potential of diseases associated with traffic. Our study highlights the public health significance of local traffic reduction policies in addressing asthma incidence in urban areas. The recommended public health actions include implementing policy interventions to reduce traffic levels and emissions in urban areas. These findings can be useful for other countries/settings facing similar issues with traffic-related air pollution and asthma incidence. The policy intervention can also positively impact other traffic-related health effects such as physical activity, noise, and availability of green spaces. Key messages • Local traffic reduction policies can significantly reduce (paediatric) asthma incidence in urban areas in large European Cities. • Reducing traffic levels reduces traffic-related air pollution and improves public health via pathways such as promoting physical activity, reducing noise, and increasing green space availability.

Tezepelumab for the treatment of severe asthma: a plain language summary of the PATHWAY and NAVIGATOR studies.

This is a summary of the results of 2 clinical studies that looked at a medicine called tezepelumab. Tezepelumab is approved in the United States of America (USA), the European Union (EU) and several other countries for the treatment of severe, uncontrolled asthma in people aged 12 and above. The results of these 2 studies, called PATHWAY and NAVIGATOR, formed the basis for tezepelumab's approval for use. Tezepelumab is a type of biologic treatment called an antibody. Biologics are treatments that target certain cells or proteins in the body and often in the immune system - the body's natural defence system against infections and diseases - to reduce patients' disease. It works by blocking a key first step in the body's chain reaction leading to inflammation in the airways of people with severe asthma. The clinical studies were done to learn if tezepelumab can be used to treat people with severe, uncontrolled asthma and to find out about its safety. In both studies, tezepelumab was compared to placebo. A placebo is a dummy treatment that looked like tezepelumab but did not have any medicine in it. In both studies, tezepelumab reduced the number of severe asthma attacks that the participants had per year compared with placebo. It also increased the volume of air that the participants could breathe out in 1second compared with placebo. Tezepelumab was well-tolerated, and a similar number of participants had health issues in the tezepelumab and placebo treatment groups. The most common health issues that the participants had during the PATHWAY study were: Worsening of asthma, common cold, headache, and inflammation of the airways. The most common health issues that the participants had during the NAVIGATOR study were: Common cold, infection of the sinuses, throat and airways, headache, worsening of asthma, and inflammation of the airways. The results showed that participants who had monthly doses of tezepelumab had fewer severe asthma attacks and better lung function than those who had placebo. In both studies, the health issues that the participants had were similar between the tezepelumab and placebo treatment groups. Overall, the studies showed that tezepelumab worked in a broad population of people with severe asthma and that the study participants had an acceptable level of health issues during the studies. These results led to the approval of tezepelumab for people with severe asthma aged 12 and above in the USA, EU and other countries. Clinical Trial Registration: PATHWAY study: NCT02054130; NAVIGATOR study: NCT03347279 (ClinicalTrials.gov).

Brain response in asthma: the role of "lung-brain" axis mediated by neuroimmune crosstalk.

In addition to typical respiratory symptoms, patients with asthma are frequently accompanied by cognitive decline, mood disorders (anxiety and depression), sleep disorders, olfactory disorders, and other brain response manifestations, all of which worsen asthma symptoms, form a vicious cycle, and exacerbate the burden on families and society. Therefore, studying the mechanism of neurological symptoms in patients with asthma is necessary to identify the appropriate preventative and therapeutic measures. In order to provide a comprehensive reference for related research, we compiled the pertinent literature, systematically summarized the latest research progress of asthma and its brain response, and attempted to reveal the possible "lung-brain" crosstalk mechanism and treatment methods at the onset of asthma, which will promote more related research to provide asthmatic patients with neurological symptoms new hope.

The relationship between PM2.5 and the onset and exacerbation of childhood asthma: a short communication.

Much is known about the link between air pollution and asthma in adults, particularly fine particulate matter (PM2.5). Studies have found that certain levels of fine PM2.5 can increase airway responsiveness and worsen asthma. PM2.5 may play a role in the onset and exacerbation of childhood asthma. However, there is little in the literature on how PM2.5 affects asthma attacks and exacerbations in children. Asthma is a common chronic disease in children, and air pollution can aggravate it. The effect of PM2.5 on childhood asthma needs further research. By evaluating, reviewing, and collating existing results in this area, this paper aims to explore the relationship between PM2.5 and asthma onset and exacerbation in children.

Gaps and Future Directions in Clinical Research on Obesity-Related Asthma.

Obesity is a major comorbidity for the development and worsening of asthma. It is associated with increased disease incidence, reduced response to inhaled and systemic steroids, increased asthma exacerbations, and poor disease control. Over the past twodecades, we have learned that there are clinical asthma phenotypes associated with obesity, which have unique immune, inflammatory, and metabolic disease mechanisms. The objectives of this review are to provide a brief overview of the associations and gaps between these chronic inflammatory diseases and the role that traditional therapies have on treating patients with obesity-related asthma, and to describe new clinical research of therapeutic developments targeting mechanisms that are more specific to this patient population.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA.Case presentationWe report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy.ConclusionTo the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Effectiveness of Intravenous Magnesium Sulfate in Children Presenting to the Emergency Department with Acute Exacerbation of Asthma

Asthma is a serious medical condition in the pediatric age group and can have a high mortality, therefore it should be managed effectively. Patients not responding adequately to first line therapy need additional treatment. A few research studies have evaluated the use of intravenous magnesium sulfate in improving respiratory scores in severe acute pediatric asthma but the results have been conflicting. Objectives: To determine the benefit of intravenous magnesium sulfate in treating children presenting with worsening of asthma symptoms. Methods: A cross-sectional prospective study carried out at the Pediatrics Unit of Zia Uddin University Hospital, Karachi from 1st March 2021 to 1st March 2022. On the whole, 280 children in the age group 2-12 years with acute worsening of asthma of were selected by non-probability purposive sampling technique, however, children in need of invasive ventilation and those having asthma related complications on radiological investigations were omitted. Chi-square was applied for categorical variables and a p-value &lt;0.05 was considered statistically significant. Results: Out of 280 patients who came to the Pediatric Emergency Department with acute severe asthma, 236 (84.3%) patients responded to a single dose of intravenous magnesium sulfate manifested by an improvement in clinical asthma score, while 44 patients (15.7%) did not show improvement. The admission rate to the pediatric intensive care unit was only 12.8%. Conclusion: Magnesium sulfate infusion helps improve respiratory symptoms in acute worsening of pediatric asthma.

A retrospective study regarding the influence of COVID-19 disease on asthma

BackgroundDuring the Covid-19 pandemic patients suffering from asthma raised many concerns regarding the outcome ofthe impact of COVID-19 disease on their preexisting condition. The 2021 GINA report indicates that people with asthma do not appear to be at increased risk of a severe form of COVID-19.MethodThis study is a retrospective study of patients (n = 163) median age = 27.8 years, M:F = 1:1.26, with asthma evaluated using ACT (asthma control test) and VAS (visual analog scale) before and after COVID-19 disease. An ACT score over 20 points placed patients in the controlled asthma group.ResultsThe overall evaluation for COVID-19 in our asthma patients revealed that 22.7% of the studied group had the COVID-19 disease (21.5% in the controlled asthma group and 24.5% in uncontrolled asthma group). Asthma disease history was longer in the uncontroled asthma group (128 ± 96.8 months vs. 296 ± 59.7 months, p = 0.05). Asthma treatment was conducted according to the GINA guideline, and 18.4% (30 pts) of the patients were on allergen immunotherapy treatment. Significantly more uncontrolled patients were significantly more in Step 1 and 5 of treatment (p = 0.05 and p = 0.03). During the COVID-19 pandemic, patients in the GINA step 5 of treatment experienced a worsening of asthma, often twice as severe as compared to patients with asthma in GINA step 1–4. In these patients, even mild COVID-19 disease led to worsened asthma symptoms, while severe COVID-19 led to a severe asthma impairment measured by ACT score (p = 0.03) and VAS scale (p = 0.02), with increased oral corticosteroids consumption.ConclusionMaintaining optimal asthma control should be able to reduce risk of severe outcomes after COVID-19 disease. Communication via phone with the specialist involved in their asthma care was very comforting for patients, thus confirming the necessity to include phone calls, smart phone’s application or online evaluations and counseling in long-term care of chronic diseases.

Steady-state estradiol triggers a unique innate immune response to allergen resulting in increased airway resistance

RationaleAsthma is a chronic airway condition that occurs more often in women than men during reproductive years. Population studies have collectively shown that long-term use of oral contraceptives decreased the onset of asthma in women of reproductive age. In the current study, we hypothesized that steady-state levels of estrogen would reduce airway inflammation and airway hyperresponsiveness to methacholine challenge.MethodsOvariectomized BALB/c mice (Ovx) were implanted with subcutaneous hormone pellets (estrogen, OVX-E2) that deliver consistent levels of estrogen [68 ± 2 pg/mL], or placebo pellets (OVX-Placebo), followed by ovalbumin sensitization and challenge. In conjunction with methacholine challenge, immune phenotyping was performed to correlate inflammatory proteins and immune populations with better or worse pulmonary outcomes measured by invasive pulmonary mechanics techniques.ResultsHistologic analysis showed an increase in total cell infiltration and mucus staining around the airways leading to an increased inflammatory score in ovarectomized (OVX) animals with steady-state estrogen pellets (OVX-E2-OVA) as compared to other groups including female-sham operated (F-INTACT-OVA) and OVX implanted with a placebo pellet (OVX-Pl-OVA). Airway resistance (Rrs) and lung elastance (Ers) were increased in OVX-E2-OVA in comparison to F-INTACT-OVA following aerosolized intratracheal methacholine challenges. Immune phenotyping revealed that steady-state estrogen reduced CD3+ T cells, CD19+ B cells, ILC2 and eosinophils in the BAL across all experiments. While these commonly described allergic cells were reduced in the BAL, or airways, we found no changes in neutrophils, CD3+ T cells or CD19+ B cells in the remaining lung tissue. Similarly, inflammatory cytokines (IL-5 and IL-13) were also decreased in OVX-E2-OVA-treated animals in comparison to Female-INTACT-OVA mice in the BAL, but in the lung tissue IL-5, IL-13 and IL-33 were comparable in OVX-E2-OVA and F-INTACT OVA mice. ILC2 were sorted from the lungs and stimulated with exogenous IL-33. These ILC2 had reduced cytokine and chemokine expression when they were isolated from OVX-E2-OVA animals, indicating that steady-state estrogen suppresses IL-33-mediated activation of ILC2.ConclusionsTherapeutically targeting estrogen receptors may have a limiting effect on eosinophils, ILC2 and potentially other immune populations that may improve asthma symptoms in those females that experience perimenstrual worsening of asthma, with the caveat, that long-term use of estrogens or hormone receptor modulators may be detrimental to the lung microenvironment over time.