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1.
J Am Board Fam Med ; 37(2): 321-323, 2024.
Article in English | MEDLINE | ID: mdl-38740479

ABSTRACT

BACKGROUND: Primary care clinicians do not adhere to national and international guidelines recommending pulmonary function testing (PFTs) in patients with suspected asthma. Little is known about why that occurs. Our objective was to assess clinician focused barriers to ordering PFTs. METHODS: An internet-based 11-item survey of primary care clinicians at a large safety-net institution was conducted between August 2021 and November 2021. This survey assessed barriers and possible electronic health record (EHR) solutions to ordering PFTs. One of the survey questions contained an open-ended question about barriers which was analyzed qualitatively. RESULTS: The survey response rate was 59% (117/200). The top 3 reported barriers included beliefs that testing will not change management, distance to testing site, and the physical effort it takes to complete testing. Clinicians were in favor of an EHR intervention to prompt them to order PFTs. Responses to the open-ended question also conveyed that objective testing does not change management. DISCUSSION: PFTs improve diagnostic accuracy and reduce inappropriate therapies. Of the barriers we identified, the most modifiable is to educate clinicians about how PFTs can change management. That in conjunction with an EHR prompt, which clinicians approved of, may lead to guideline congruent and improved quality in asthma care.


Subject(s)
Asthma , Guideline Adherence , Practice Patterns, Physicians' , Primary Health Care , Respiratory Function Tests , Humans , Asthma/diagnosis , Asthma/physiopathology , Practice Patterns, Physicians'/statistics & numerical data , Guideline Adherence/statistics & numerical data , Adult , Electronic Health Records/statistics & numerical data , Surveys and Questionnaires , Male , Female , Practice Guidelines as Topic , Attitude of Health Personnel , Physicians, Primary Care/statistics & numerical data , Middle Aged
2.
BMC Pulm Med ; 24(1): 230, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730359

ABSTRACT

BACKGROUND: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. METHODS: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).


Subject(s)
Asthma , Cross-Over Studies , Pulmonary Disease, Chronic Obstructive , Spirometry , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Asthma/diagnosis , Asthma/physiopathology , Male , Middle Aged , Spirometry/instrumentation , Female , Adult , Forced Expiratory Volume , Vital Capacity , Aged , India , Young Adult
3.
J Assoc Physicians India ; 72(3): 55-62, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38736118

ABSTRACT

The Global Lung Initiative (GLI) race-neutral equations are considered to be race agnostic, using inverse probability weight, and have lower limits of normality (LLN) different from the GLI mixed equations. In this observational study, we analyzed the impact of using GLI equations to interpret spirometry of 1,169 patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), COPD suspects, small airway obstruction, posttubercular lung disease, and preserved ratio with impaired spirometry (PRISm) (46% females, average age 46 years). Predicted normal and the LLN using GLI equations were significantly higher than those using Indian equations. The GLI race-neutral equations changed the category in 35.17% of males and 42.64% of females compared to Indian equations. The GLI mixed equations categorized a greater percentage of patients to have a mixed ventilatory pattern compared to the GLI race-neutral equations. There was a significant change in the grading of the severity of COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages based on the percentage of predicted values of FEV1. Although GLI race-neutral equations have greater concordance with Indian equations than GLI Mixed equations, these substantially overdiagnose abnormal ventilatory patterns on spirometry in adult Indians in western India with chronic respiratory disease. A substantial number of patients with normal or obstructive patterns on spirometry are recategorized to have mixed or restrictive patterns. The use of GLI race-neutral equations increases the severity of airflow limitation in COPD patients. GLI race-neutral predictions for FEV1 result in substantially fewer patients demonstrating postbronchodilator responsiveness (PBDR).


Subject(s)
Pulmonary Disease, Chronic Obstructive , Spirometry , Humans , Male , Female , Middle Aged , India , Spirometry/methods , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/ethnology , Pulmonary Disease, Chronic Obstructive/diagnosis , Adult , Forced Expiratory Volume , Asthma/physiopathology , Asthma/diagnosis , Asthma/ethnology , Chronic Disease , Severity of Illness Index
4.
BMJ Open Respir Res ; 11(1)2024 May 02.
Article in English | MEDLINE | ID: mdl-38697675

ABSTRACT

BACKGROUND: Methods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N2SBW) and nitrogen multiple breath washout (N2MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N2SBW and N2MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in SIII at N2SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV1) in MCT. STUDY DESIGN AND METHODS: This prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N2SBW (SIII), N2MBW (Lung clearance index (LCI), Scond, Sacin), MCT (FEV1 and sGeff) as well as N2SBW between each methacholine dose. RESULTS: 182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N2SBW was pathological in 10.6% at baseline and N2MBW abnormality ranged widely (LCI 81%, Scond 18%, Sacin 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N2SBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with N2MBW. CONCLUSIONS: Both MCT and N2 washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.


Subject(s)
Asthma , Breath Tests , Bronchial Provocation Tests , Methacholine Chloride , Nitrogen , Spirometry , Humans , Asthma/diagnosis , Asthma/physiopathology , Methacholine Chloride/administration & dosage , Female , Male , Prospective Studies , Adult , Breath Tests/methods , Middle Aged , Nitrogen/analysis , Bronchial Provocation Tests/methods , Forced Expiratory Volume , Respiratory Function Tests/methods , Lung/physiopathology , Bronchoconstrictor Agents/administration & dosage
5.
BMC Pulm Med ; 24(1): 244, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760654

ABSTRACT

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.


Subject(s)
Asthma , Nitric Oxide , Spirometry , Humans , Asthma/drug therapy , Asthma/metabolism , Asthma/diagnosis , Asthma/physiopathology , Pilot Projects , Male , Female , Adult , Middle Aged , Nitric Oxide/analysis , Nitric Oxide/metabolism , Forced Expiratory Volume , Fractional Exhaled Nitric Oxide Testing , Circadian Rhythm , Sputum/metabolism , Eosinophils/metabolism , Exhalation , Breath Tests/methods
6.
BMC Pulm Med ; 24(1): 214, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698432

ABSTRACT

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.


Subject(s)
Asthma , Spirometry , Humans , Male , Female , Asthma/physiopathology , Asthma/therapy , Asthma/diagnosis , Forced Expiratory Volume , Middle Aged , Adult , Nitric Oxide/analysis , Nitric Oxide/metabolism , Aged , Fractional Exhaled Nitric Oxide Testing
7.
Ter Arkh ; 96(3): 240-245, 2024 Apr 16.
Article in Russian | MEDLINE | ID: mdl-38713038

ABSTRACT

AIM: To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. MATERIALS AND METHODS: We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. RESULTS: The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. CONCLUSION: Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.


Subject(s)
Asthma , Humans , Asthma/drug therapy , Asthma/physiopathology , Male , Female , Middle Aged , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/therapeutic use , Severity of Illness Index , Quality of Life , Respiratory Function Tests/methods , Treatment Outcome , Aged , Biological Therapy/methods , Biological Therapy/adverse effects , Young Adult , Adolescent
8.
Ter Arkh ; 96(3): 246-252, 2024 Apr 16.
Article in Russian | MEDLINE | ID: mdl-38713039

ABSTRACT

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Asthma/physiopathology , Middle Aged , Work of Breathing/physiology , Lung/physiopathology , Adult , Elasticity , Respiratory Function Tests/methods , Bronchodilator Agents/pharmacology , Bronchodilator Agents/administration & dosage
9.
BMC Pediatr ; 24(1): 296, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702638

ABSTRACT

BACKGROUND: Cough variant asthma (CVA) is one of the most common causes of chronic cough in children worldwide. The diagnosis of CVA in children remains challenging. This study aimed to assess the diagnostic utility of impulse oscillometry (IOS) pulmonary function in children with CVA. METHODS: This study included children aged 4 to 12 years diagnosed with CVA who underwent IOS pulmonary function and bronchodilation (BD) tests. A control group of healthy children was matched. Pre- and post-BD IOS parameters were recorded and presented as mean ± standard deviation or median. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to evaluate the discriminatory potential of the IOS parameters for diagnosing CVA. RESULTS: A total of 180 patients with CVA and 65 control subjects were included. The baseline IOS parameters in the CVA group, except X5%pred, were significantly greater compared to the control group. After inhalation of salbutamol sulfate, all IOS parameters improved significantly in the CVA group. However, Z5%pred, R5%pred, and R20%pred remained greater in the CVA group compared to the control group. The improvement rates of IOS parameters in the CVA group significantly surpassed those in the control group. The ROC curve results for pre-BD IOS parameters and the improvement rate during the BD test showed that the combinations of pre-Z5%pred+△Z5% and pre-R5%pred+△R5% achieved the highest AUC value of 0.920 and 0.898, respectively. The AUC values of these combined parameters surpassed those of individual ones. CONCLUSIONS: This study highlights that children with CVA exhibit greater IOS parameters compared to healthy children. The changes in IOS parameters during the BD test provided valuable diagnostic information for CVA, and the combination of various parameters can help pediatricians accurately identify CVA in children.


Subject(s)
Asthma , Cough , Oscillometry , Humans , Cough/etiology , Cough/diagnosis , Child , Asthma/diagnosis , Asthma/physiopathology , Male , Female , Oscillometry/methods , Child, Preschool , Case-Control Studies , ROC Curve , Albuterol , Respiratory Function Tests/methods , Bronchodilator Agents , Cough-Variant Asthma
10.
Respir Res ; 25(1): 194, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702779

ABSTRACT

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.


Subject(s)
Asthma , Humans , Asthma/diagnosis , Asthma/therapy , Asthma/physiopathology , Asthma/epidemiology , Child , Spirometry/methods , Monitoring, Physiologic/methods , Disease Management , Fractional Exhaled Nitric Oxide Testing/methods
11.
Science ; 384(6691): 66-73, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38574138

ABSTRACT

Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.


Subject(s)
Asthma , Bronchi , Bronchoconstriction , Animals , Humans , Mice , Asthma/pathology , Asthma/physiopathology , Bronchoconstriction/drug effects , Inflammation/pathology , Signal Transduction , Ion Channels/antagonists & inhibitors , Lysophospholipids/antagonists & inhibitors , Sphingosine/analogs & derivatives , Sphingosine/antagonists & inhibitors , Bronchi/pathology , Bronchi/physiopathology
12.
Respir Res ; 25(1): 178, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658975

ABSTRACT

Severe asthma is associated with an increased risk for exacerbations, reduced lung function, fixed airflow obstruction, and substantial morbidity and mortality. The concept of remission in severe asthma as a new treatment goal has recently gained attention due to the growing use of monoclonal antibody therapies, which target specific pathologic pathways of inflammation. This review evaluates the current definitions of asthma remission and unveils some of the barriers for achieving this state in the severe asthma population. Although there is no unified definition, the concept of clinical remission in asthma should be based on a sustained period of symptom control, elimination of oral corticosteroid exposure and exacerbations, and stabilization of pulmonary function. The conjugation of these criteria seems a realistic treatment target in a minority of asthmatic patients. Some unmet needs in severe asthma may affect the achievement of clinical remission. Late intervention with targeted therapies in the severe asthma population may increase the risk of corticosteroid exposure and the development of irreversible structural airway changes. Moreover, airway infection is an important component in persistent exacerbations in patients on biologic therapies. Phenotyping exacerbations may be useful to guide therapy decisions and to avoid the liberal use of oral corticosteroids. Another challenge associated with the aim of clinical remission in severe asthma is the multifaceted interaction between the disease and its associated comorbidities. Behavioural factors should be evaluated in case of persistent symptoms despite optimised treatment, and assessing biomarkers and targeting treatable traits may allow for a more objective way of reaching remission. The concept of clinical remission will benefit from an international consensus to establish unifying criteria for its assessment, and it should be addressed in the future management guidelines.


Subject(s)
Anti-Asthmatic Agents , Asthma , Remission Induction , Severity of Illness Index , Humans , Asthma/drug therapy , Asthma/diagnosis , Asthma/physiopathology , Asthma/epidemiology , Remission Induction/methods , Anti-Asthmatic Agents/therapeutic use , Treatment Outcome
13.
J Theor Biol ; 588: 111835, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38643962

ABSTRACT

Obesity is a contributing factor to asthma severity; while it has long been understood that obesity is related to greater asthma burden, the mechanisms though which this occurs have not been fully elucidated. One common explanation is that obesity mechanically reduces lung volume through accumulation of adipose tissue external to the thoracic cavity. However, it has been recently demonstrated that there is substantial adipose tissue within the airway wall itself, and that the presence of adipose tissue within the airway wall is related to body mass index. This suggests the possibility of an additional mechanism by which obesity may worsen asthma, namely by altering the behaviour of the airways themselves. To this end, we modify Anafi & Wilson's classic model of the bistable terminal airway to incorporate adipose tissue within the airway wall in order to answer the question of how much adipose tissue would be required in order to drive substantive functional changes. This analysis suggests that adipose tissue within the airway wall on the order of 1%-2% of total airway cross-sectional area could be sufficient to drive meaningful changes, and further that these changes may interact with volume effects to magnify the overall burden.


Subject(s)
Adipose Tissue , Asthma , Models, Biological , Obesity , Adipose Tissue/metabolism , Humans , Asthma/physiopathology , Obesity/physiopathology , Obesity/metabolism , Lung/physiology
14.
Clin Immunol ; 263: 110228, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663494

ABSTRACT

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.


Subject(s)
Airway Remodeling , Asthma , Bronchi , Eosinophil Peroxidase , Epithelial Cells , Epithelial-Mesenchymal Transition , Transforming Growth Factor beta1 , Humans , Asthma/metabolism , Asthma/pathology , Asthma/physiopathology , Asthma/immunology , Male , Female , Epithelial Cells/metabolism , Eosinophil Peroxidase/metabolism , Transforming Growth Factor beta1/metabolism , Middle Aged , Adult , Bronchi/pathology , Interleukin-5/metabolism , Chromones/pharmacology , Cytokines/metabolism , Cell Line , Thymic Stromal Lymphopoietin , Cell Proliferation , Cell Movement , Morpholines/pharmacology , ADAM Proteins
15.
Eur Respir Rev ; 33(172)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38657997

ABSTRACT

BACKGROUND: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab. METHODS: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety. RESULTS: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile. CONCLUSIONS: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.


Subject(s)
Anti-Asthmatic Agents , Asthma , Randomized Controlled Trials as Topic , Severity of Illness Index , Humans , Asthma/drug therapy , Asthma/physiopathology , Asthma/diagnosis , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/adverse effects , Treatment Outcome , Biological Products/therapeutic use , Biological Products/adverse effects , Quality of Life , Lung/drug effects , Lung/physiopathology , Female , Male , Disease Progression
18.
Int J Immunopathol Pharmacol ; 38: 3946320241246713, 2024.
Article in English | MEDLINE | ID: mdl-38649141

ABSTRACT

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.


Subject(s)
Asthma , Nitric Oxide , Obesity , Overweight , Humans , Asthma/physiopathology , Asthma/metabolism , Asthma/diagnosis , Aged , Male , Female , Retrospective Studies , Obesity/physiopathology , Obesity/metabolism , Overweight/physiopathology , Overweight/metabolism , Nitric Oxide/metabolism , Nitric Oxide/analysis , Respiratory Function Tests , Fractional Exhaled Nitric Oxide Testing , China/epidemiology , Bronchial Provocation Tests , Body Mass Index , Asian People , Respiratory Hypersensitivity/physiopathology , Respiratory Hypersensitivity/metabolism , Respiratory Hypersensitivity/diagnosis , Breath Tests
19.
BMC Pediatr ; 24(1): 284, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678177

ABSTRACT

BACKGROUND: Asthma is one of the most common chronic airway diseases in children. Preventing asthma exacerbation is one of the objectives of all asthma action plans. In patients with poor perception, it is difficult to identify acute asthma exacerbations by clinical asthma score, asthma control test or asthma control questionnaire. The aim of this study is to analyze whether children with asthma have changes in peak expiratory flow(PEF)before an acute asthma exacerbation and to evaluate the relationship between PEF and asthma exacerbation. METHODS: Basic information (including sex, age, atopy, etc.) and clinical information of asthmatic children who registered in the Electronic China Children's Asthma Action Plan (e-CCAAP) from 1 September 2017 to 31 August 2021 were collected. Subjects with 14 consecutive days of PEF measurements were eligible. Subjects in this study were divided into an exacerbation group and a control group. We analyzed the relationship between changes in PEF% pred and the presence of asthma symptoms. RESULT: A total of 194 children with asthma who met the inclusion criteria were included, including 144 males (74.2%) and 50 females (25.8%), with a male-to-female ratio of 2.88:1. The mean age of the subjects was 9.51 ± 2.5 years. There were no significant differences in sex, age, allergy history or baseline PEF between the two groups. In children with and without a history of allergy, there was no significant difference between the variation in PEF at 14 days. Patients who only had a reduced in PEF but no symptoms of asthma exacerbation had the greatest reduction in PEF compared to the other groups. The most common cause of acute exacerbations of asthma is upper respiratory tract infection. Among the causes of acute exacerbations of asthma, the variation in PEF caused by air pollution was significantly higher than that of other causes (P < 0.05). In acute exacerbations, the decrease in PEF was significantly greater in the exacerbation group than in the control group. In children with asthma symptoms, there was a decrease in PEF approximately 1.34 days before the onset of symptoms. CONCLUSION: Children with asthma show a decrease in PEF 1.34 days before the onset of asthma symptoms. We recommend that asthmatic children who show a decrease in PEF should step-up asthma therapy. The most common cause of acute exacerbations of asthma was upper respiratory tract infections, and the variation in PEF caused by air pollution was significantly higher than that caused by other factors.


Subject(s)
Asthma , Disease Progression , Humans , Asthma/physiopathology , Asthma/complications , Female , Male , Child , Peak Expiratory Flow Rate , China/epidemiology , Adolescent
20.
Expert Opin Pharmacother ; 25(4): 383-393, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38497368

ABSTRACT

INTRODUCTION: The pharmacotherapy of asthma is a dynamic process that changes as our knowledge of the underlying pathophysiology and treatment of this disease continues to evolve. This implies the need for continuous revision of the recommendations of asthma guidelines and strategies. AREAS COVERED: This review summarizes the latest key practical information on the pharmacological management of asthma in adults. We provide the background to the 2023 update of the GINA strategy report, focusing on changes and discussing areas of uncertainty. We review current and emerging pharmacotherapy for uncontrolled asthma, including synthetic agents and new biologics, and provide expert perspectives and opinions on the treatment of uncontrolled asthma. EXPERT OPINION: The current pharmacological treatment of asthma, based on a step-by-step, control-based approach, with ICSs, LABAs and LAMAs being the mainstay generally provides good symptom control. Biologic therapies are often effective in treating T2high severe asthma. However, there is still room for improvement, such as the discovery of new molecules that specifically target chronic inflammation and, most importantly, the ability to provide solutions to the various areas of uncertainty that still exist. Also finding solutions to improve the accessibility and affordability of rescue ICS in resource-constrained settings is critical.


Subject(s)
Anti-Asthmatic Agents , Asthma , Practice Guidelines as Topic , Humans , Asthma/drug therapy , Asthma/physiopathology , Anti-Asthmatic Agents/therapeutic use , Adult , Biological Products/therapeutic use , Severity of Illness Index , Administration, Inhalation
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