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1.
Ther Adv Respir Dis ; 18: 17534666241254980, 2024.
Article in English | MEDLINE | ID: mdl-38804685

ABSTRACT

BACKGROUND: Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. OBJECTIVES: To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). DESIGN: This was a single-center, retrospective, observational cohort study. METHODS: We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. RESULTS: Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). CONCLUSION: BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.


Subject(s)
Asthma , Bronchial Thermoplasty , Lung , Severity of Illness Index , Humans , Male , Retrospective Studies , Female , Bronchial Thermoplasty/adverse effects , Asthma/physiopathology , Asthma/therapy , Middle Aged , Forced Expiratory Volume , Treatment Outcome , Aged , Lung/physiopathology , Adult , Recovery of Function , Time Factors , Quality of Life
3.
Acta Biochim Biophys Sin (Shanghai) ; 56(5): 730-739, 2024 05 25.
Article in English | MEDLINE | ID: mdl-38655617

ABSTRACT

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.


Subject(s)
AMP-Activated Protein Kinases , Airway Remodeling , Apoptosis , Autophagy , Bronchial Thermoplasty , Myocytes, Smooth Muscle , Signal Transduction , TOR Serine-Threonine Kinases , TOR Serine-Threonine Kinases/metabolism , Humans , Autophagy/drug effects , AMP-Activated Protein Kinases/metabolism , Bronchial Thermoplasty/methods , Myocytes, Smooth Muscle/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Asthma/metabolism , Asthma/pathology , Male , Cells, Cultured , Bronchi/metabolism , Bronchi/pathology , Aminoimidazole Carboxamide/analogs & derivatives , Ribonucleotides
4.
Respir Med ; 225: 107583, 2024.
Article in English | MEDLINE | ID: mdl-38447787

ABSTRACT

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma. Although multiple trials have demonstrated clinical improvement after BT, optimal patient selection remains a challenge and the mechanism of action is incompletely understood. The aim of this study was to examine whether exhaled breath analysis can contribute to discriminate between BT-responders and non-responders at baseline and to explore pathophysiological insights of BT. METHODS: Exhaled breath was collected from patients at baseline and six months post-BT. Patients were defined as responders or non-responders based on a half point increase in asthma quality of life questionnaire scores. Gas chromatography-mass spectrometry was used for volatile organic compounds (VOCs) detection and analyses. Analytical workflow consisted of: 1) detection of VOCs that differentiate between responders and non-responders and those that differ between baseline and six months post-BT, 2) identification of VOCs of interest and 3) explore correlations between clinical biomarkers and VOCs. RESULTS: Data was available from 14 patients. Nonanal, 2-ethylhexanol and 3-thujol showed a significant difference in intensity between responders and non-responders at baseline (p = 0.04, p = 0.01 and p = 0.03, respectively). After BT, no difference was found in the compound intensity of these VOCs. A negative correlation was observed between nonanal and IgE and BALF eosinophils (r = -0.68, p < 0.01 and r = -0.61, p = 0.02 respectively) and 3-thujol with BALF neutrophils (r = -0.54, p = 0.04). CONCLUSIONS: This explorative study identified discriminative VOCs in exhaled breath between BT responders and non-responders at baseline. Additionally, correlations were found between VOC's and inflammatory BALF cells. Once validated, these findings encourage research in breath analysis as a non-invasive easy to apply technique for identifying airway inflammatory profiles and eligibility for BT or immunotherapies in severe asthma.


Subject(s)
Aldehydes , Asthma , Bicyclic Monoterpenes , Bronchial Thermoplasty , Volatile Organic Compounds , Humans , Bronchial Thermoplasty/methods , Quality of Life , Volatile Organic Compounds/analysis
5.
Thorax ; 79(4): 359-362, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38346871

ABSTRACT

The mechanism of action of bronchial thermoplasty (BT) treatment for patients with severe asthma is incompletely understood. This study investigated the 2.5-year impact of BT on airway smooth muscle (ASM) mass and clinical parameters by paired data analysis in 22 patients. Our findings demonstrate the persistence of ASM mass reduction of >50% after 2.5 years. Furthermore, sustained improvement in asthma control, quality of life and exacerbation rates was found, which is in line with previous reports. An association was found between the remaining ASM and both the exacerbation rate (r=0.61, p=0.04 for desmin, r=0.85, p<0.01 for alpha smooth muscle actin (SMA)) and post-bronchodilator forced expiratory volume in 1 s predicted percentage (r=-0.69, p=0.03 for desmin, r=-0.58, p=0.08 for alpha SMA). This study provides new insight into the long-term impact of BT.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Bronchi/surgery , Quality of Life , Desmin/therapeutic use , Asthma/drug therapy , Treatment Outcome , Muscle, Smooth
6.
Arerugi ; 73(1): 40-51, 2024.
Article in Japanese | MEDLINE | ID: mdl-38403700

ABSTRACT

BACKGROUND AND AIMS: Bronchial thermoplasty (BT) is a bronchoscopic treatment for adult patients with moderate to severe asthma. A systematic review was conducted to examine the efficacy of this treatment. METHODS: Randomized controlled comparing BT to a control in adult patients with moderate to severe asthma were added to the previously conducted systematic review. Literature published prior to July 2022 was selected. RESULTS: Four trials were included in this study. BT resulted in significant improvement in quality of life. However, no significant difference in asthma control was observed. Moreover, the incidence of severe adverse events during the treatment period was increased by BT. Furthermore, BT did not improve lung function, increase withdrawal from oral corticosteroids, reduce frequency of rescue medication usage, or increase the number of symptom-free days. CONCLUSION: From a risk-benefit perspective, there is insufficient evidence to support a recommendation of BT in adult patients with moderate to severe asthma.


Subject(s)
Asthma , Bronchial Thermoplasty , Adult , Humans , Quality of Life , Asthma/surgery , Asthma/drug therapy , Adrenal Cortex Hormones/therapeutic use
7.
Chest ; 165(2): e27-e31, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38336440

ABSTRACT

Irritant-induced asthma (IIA) may develop after acute inhalational exposure in individuals without preexisting asthma. The effect of bronchial thermoplasty to treat intractable, worsening IIA has not yet been described. We evaluated a previously healthy 52-year-old man after inhalation of an unknown white powder. His pulmonary function and symptoms/quality of life worsened over 4 years, despite maximal guidelines-based asthma therapy. We acquired 129Xe MRI and pulmonary function test measurements on three occasions including before and after bronchial thermoplasty treatment. Seven months after bronchial thermoplasty, improved MRI ventilation and oscillometry small airway resistance were observed. Spirometry and asthma control did not improve until 19 months after bronchial thermoplasty, 5.5 years postexposure. Together, oscillometry measurements of the small airways and 129Xe MRI provided effort-independent, sensitive, and objective measurements of response to therapy. Improved MRI and oscillometry small airway resistance measurements temporally preceded improved airflow obstruction and may be considered for complex asthma cases.


Subject(s)
Asthma , Bronchial Thermoplasty , Male , Humans , Middle Aged , Bronchial Thermoplasty/adverse effects , Irritants , Quality of Life , Oscillometry , Magnetic Resonance Imaging
8.
J Allergy Clin Immunol ; 153(2): 435-446.e4, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37805024

ABSTRACT

BACKGROUND: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling. OBJECTIVE: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes. METHODS: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored. RESULTS: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 µm to 5.74 µm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility. CONCLUSIONS: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Bronchi/surgery , Bronchi/pathology , Airway Remodeling , Asthma/drug therapy , Extracellular Matrix/pathology , Collagen
9.
Chest ; 165(4): 775-784, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38123124

ABSTRACT

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Asthma/drug therapy , Bronchial Thermoplasty/adverse effects , Bronchial Thermoplasty/methods , Longitudinal Studies , Prospective Studies , Quality of Life , Tomography, X-Ray Computed
10.
Respir Res ; 24(1): 294, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996952

ABSTRACT

RATIONALE: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression, cytokine production and metabolic profile. Despite these observations, biological mechanisms explaining asthma control improvement post-BT are still not well understood. OBJECTIVES: To assess whether BT affects gene signatures in bronchial epithelial cells (BECs). METHODS: In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment. MEASUREMENTS AND MAIN RESULTS: Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human ß-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33. CONCLUSIONS: These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Thymic Stromal Lymphopoietin , Alarmins , Toll-Like Receptor 4 , Asthma/genetics , Asthma/surgery , Asthma/metabolism , Cytokines/metabolism
12.
Eur J Med Res ; 28(1): 331, 2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37689769

ABSTRACT

OBJECTIVES: To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating patients with chronic obstructive pulmonary disease (COPD). METHODS: Clinical data of 57 COPD patients were randomized into the control (n = 29, conventional inhalation therapy) or intervention group (n = 28, conventional inhalation therapy plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, modified Medical Research Council (mMRC), 6-min walk test (6MWT), COPD assessment test (CAT) score and acute exacerbation incidence from baseline to an average of 3 and 12 months. Safety was assessed by adverse events. RESULTS: FEV1, FEV1(%, predicted) and FVC in both groups improved to varying degrees post-treatment compared with those pre-treatment (P < 0.05). The Intervention group showed greater improving amplitudes of FEV1 (Ftime × between groups = 21.713, P < 0.001) and FEV1(%, predicted) (Ftime × between groups = 31.216, P < 0.001) than the control group, and there was no significant difference in FVC variation trend (Ftime × between groups = 1.705, P = 0.193). mMRC, 6MWT and CAT scores of both groups post-treatment improved to varying degrees (Ps < 0.05), but the improving amplitudes of mMRC (Ftime × between groups = 3.947, P = 0.025), 6MWT (Ftime × between groups = 16.988, P < 0.001) and CAT score (Ftime × between groups = 16.741, P < 0.001) in the intervention group were greater than the control group. According to risk assessment of COPD acute exacerbation, the proportion of high-risk COPD patients with acute exacerbation in the control and intervention groups at 1 year post-treatment (100% vs 65%, 100% vs 28.6%), inpatient proportion (100% vs 62.1%; 100% vs 28.6%), COPD acute exacerbations [3.0 (2.50, 5.0) vs 1.0 (1.0, 2.50); 3.0(3.0, 4.0) vs 0 (0, 1.0)] and hospitalizations [2.0 (2.0, 3.0) vs 1.0 (0, 2.0); 2.0 (2.0, 3.0) vs 0 (0, 1.0)] were significantly lower than those pre-treatment (P < 0.05). Besides, data of the intervention group were significantly lower than the control group at each timepoint after treatment (P < 0.05). CONCLUSIONS: Combined BT therapy is superior to conventional medical treatment in improving lung function and quality of life of COPD patients, and it also significantly reduces the COPD exacerbation risk without causing serious adverse events.


Subject(s)
Bronchial Thermoplasty , Pulmonary Disease, Chronic Obstructive , Humans , Hospitalization , Inpatients , Pulmonary Disease, Chronic Obstructive/surgery , Quality of Life
13.
Respir Investig ; 61(6): 675-681, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37708632

ABSTRACT

Bronchial thermoplasty is the only device-based nonpharmacological treatment approach for severe asthma. Current guidelines are cautious in recommending bronchial thermoplasty because of unknown patient response prediction. Recent research on bronchial thermoplasty includes up-to-date, state-of-the-art, and recent-advances reviews. However, these reviews provide a broad and general discussion on equipment, technique, patient selection, and patient management, with little evaluation of the predictors of a beneficial response. Predicting an optimal response to bronchial thermoplasty in patients with severe asthma remains elusive. The lack of reliable predictive markers means that bronchial thermoplasty remains a last-line treatment and makes profiling for predicting the response or efficacy a topic of study. Genetic changes are associated with airway remodeling. A gap in the literature exists regarding patient profiling to predict the response to bronchial thermoplasty in patients with severe asthma. Therefore, recently published omics data and genetic associations regarding the response to bronchial thermoplasty therapy should be reviewed. We present an up-to-date review of recent publications profiling the response to bronchial thermoplasty in patients with severe asthma.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Bronchial Thermoplasty/methods , Asthma/genetics , Asthma/surgery
14.
Respirology ; 28(11): 1053-1059, 2023 11.
Article in English | MEDLINE | ID: mdl-37550800

ABSTRACT

BACKGROUND AND OBJECTIVE: Outside clinical trials, there is limited long-term data following bronchial thermoplasty (BT). In a cohort of real-world severe asthmatics in an era of biological therapy, we sought to evaluate the safety and efficacy of BT 5 years post-treatment. METHODS: Every patient treated with BT at two Australian tertiary centres were recalled at 5 years, and evaluated by interview and record review, Asthma Control Questionnaire (ACQ), spirometry and high-resolution CT Chest. CT scans were interpreted using the modified Reiff and BRICS CT scoring systems for bronchiectasis. RESULTS: Fifty-one patients were evaluated. At baseline, this cohort had a mean age of 59.0 ± 11.8 years, mean ACQ of 3.0 ± 1.0, mean FEV1 of 55.5 ± 18.8% predicted, and 53% were receiving maintenance oral steroids in addition to triple inhaler therapy. At 5 years, there was a sustained improvement in ACQ scores to 1.8 ± 1.0 (p < 0.001). Steroid requiring exacerbation frequency was reduced from 3.8 ± 3.6 to 1.0 ± 1.6 exacerbations per annum (p < 0.001). 44% of patients had been weaned off oral steroids. No change in spirometry was observed. CT scanning identified minor degrees of localized radiological bronchiectasis in 23/47 patients with the modified Reiff score increasing from 0.6 ± 2.6 at baseline to 1.3 ± 2.5 (p < 0.001). However, no patients exhibited clinical features of bronchiectasis, such as recurrent bacterial infection. CONCLUSION: Sustained clinical benefit from BT at 5 years was demonstrated in this cohort of very severe asthmatics. Mild, localized radiological bronchiectasis was identified in a portion of patients without clinical features of bronchiectasis.


Subject(s)
Asthma , Bronchial Thermoplasty , Bronchiectasis , Humans , Middle Aged , Aged , Bronchial Thermoplasty/adverse effects , Bronchial Thermoplasty/methods , Adrenal Cortex Hormones/therapeutic use , Australia , Asthma/drug therapy , Bronchiectasis/diagnostic imaging , Bronchiectasis/surgery , Bronchiectasis/drug therapy , Steroids/therapeutic use
15.
Respir Med ; 217: 107341, 2023 10.
Article in English | MEDLINE | ID: mdl-37429559

ABSTRACT

RATIONALE: Bronchial thermoplasty (BT) reduces severity and frequency of bronchoconstriction and symptoms in severe, persistent asthmatics although it is usually not associated with change in spirometric variables. Other than spirometry. there are almost no data on changes in lung mechanics following BT. OBJECTIVE: To assess lung static and dynamic lung compliance (Cst,L and Cdyn,L, respectively) and static and dynamic lung resistance (Rst,L and Rdyn,L, respectively) before and after BT in severe asthmatics using the esophageal balloon technique. METHODS: Rdyn,L and Cdyn,L were measured at respiratory frequencies up to 145 breaths/min, using the esophageal balloon technique in 7 patients immediately before and 12-50 weeks after completing a series of 3 BT sessions. RESULTS: All patients experienced improved symptoms within a few weeks following completion of BT. Pre-BT, all patients exhibited frequency dependency of lung compliance, with mean Cdyn,L decreasing to 63% of Cst,L at maximum respiratory rates. Post-BT, Cst,L did not change significantly from pre-thermoplasty values, while Cdyn,L diminished to 62%% of Cst,L. In 4 of 7 patients, post-BT values of Cdyn,L were consistently higher than pre-BT over the range of respiratory rates. RL in 4 of 7 patients during quiet breathing and at higher respiratory frequencies decreased following BT. CONCLUSIONS: Patients with severe persistent asthma exhibit increased resting lung resistance and frequency dependence of compliance, the magnitudes of which are ameliorated in some patients following bronchial thermoplasty and associated with variable change in frequency dependence of lung resistance. These findings are related to asthma severity and may be related to the heterogeneous and variable nature of airway smooth muscle modeling and its response to BT.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Bronchial Thermoplasty/methods , Lung Compliance , Asthma/surgery , Asthma/diagnosis , Lung/surgery , Lung/physiology , Spirometry
16.
Respir Med ; 217: 107340, 2023 10.
Article in English | MEDLINE | ID: mdl-37422022

ABSTRACT

INTRODUCTION: Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in airway smooth muscle is arguably the most widely discussed mechanisms accounting for these clinical benefits. Yet, this smooth muscle reduction should also translate into an impaired response to bronchodilator drugs. This study was designed to address this question. METHODS: Eight patients with clinical indication for thermoplasty were studied. They were uncontrolled severe asthmatics despite optimal environmental control, treatment of comorbidities, and the use of high-dose inhaled corticosteroids and long-acting ß2-agonists. Lung function measured by spirometry and respiratory mechanics measured by oscillometry were examined pre- and post-bronchodilator (salbutamol, 400 µg), both before and at least 1 year after thermoplasty. RESULTS: Consistent with previous studies, thermoplasty yielded no benefits in terms of baseline lung function and respiratory mechanics, despite improving symptoms based on two asthma questionnaires (ACQ-5 and ACT-5). The response to salbutamol was also not affected by thermoplasty based on spirometric readouts, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. However, a significant interaction was observed between thermoplasty and salbutamol for two oscillometric readouts, namely reactance at 5 Hz (Xrs5) and reactance area (Ax), showing an attenuated response to salbutamol after thermoplasty. CONCLUSIONS: Thermoplasty attenuates the response to a bronchodilator. We argue that this result is a physiological proof of therapeutic efficacy, consistent with the well-described effect of thermoplasty in reducing the amount of airway smooth muscle.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Asthma/drug therapy , Asthma/surgery , Asthma/diagnosis , Albuterol/pharmacology , Albuterol/therapeutic use , Adrenal Cortex Hormones , Forced Expiratory Volume
17.
Respir Med ; 216: 107303, 2023 09.
Article in English | MEDLINE | ID: mdl-37307903

ABSTRACT

BACKGROUND: Cough is a troublesome symptom of asthma because it is associated with disease severity and poor asthma control. Bronchial thermoplasty (BT) may be effective in improving cough severity and cough-related quality of life in severe uncontrolled asthma. OBJECTIVE: To evaluate the efficacy of BT for cough in severe uncontrolled asthma. METHODS: Twelve patients with severe uncontrolled asthma were enrolled in this study between 2018 May and March 2021 and arbitrarily divided into cough-predominant [cough severity Visual Analog Scale (VAS) ≥ 40 mm, n = 8] and typical asthma (cough VAS <40 mm, n = 4) groups. Clinical parameters, such as capsaicin cough sensitivity [C-CS: the concentrations to inhaled capsaicin required to induce at least two (C2) and five (C5) coughs], lung function, and type-2-related biomarkers (fractional nitric oxides and absolute eosinophil counts) and cough-related indices [cough severity VAS and the Leicester Cough Questionnaire (LCQ)] were evaluated before and 3 months after performing BT. RESULTS: BT significantly improved both cough-related indices and C-CS in the cough-predominant group. Changes in C-CS were significantly correlated with changes in the LCQ scores (C5: r = 0.65, p = 0.02 for all patients, and r = 0.81, p = 0.01 for the cough-predominant group). CONCLUSIONS: BT may be effective for cough in severe uncontrolled asthma by improving C-CS. However, further larger cohort studies are necessary to confirm the effect of BT for cough in asthma. CLINICAL TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (Registry ID UMIN: 000031982).


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Cough/etiology , Cough/surgery , Capsaicin , Quality of Life , Asthma/drug therapy
18.
Respir Med ; 216: 107302, 2023 09.
Article in English | MEDLINE | ID: mdl-37257786

ABSTRACT

BACKGROUND: Bronchial thermoplasty (BT) has shown favorable safety and efficacy in several randomized controlled trials (RCTs), but has not been directly compared to biological therapies. METHODS: Electronic literature searches were performed on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, to retrieve RCTs of BT or FDA-approved biologicals against controls in patients with severe asthma. Six outcomes were analyzed: Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), the number of patients experiencing ≥1 asthma exacerbation, annualized exacerbation rate ratio (AERR), oral corticosteroid dose reduction (OCDR), and morning peak expiratory flow rate (amPEF). Random-effects, Frequentist network meta-analysis (NMA) were performed, and therapies were ranked using P-scores. RESULTS: Twenty-nine RCTs (15,547 patients) were included. Fewer patients treated with BT experienced ≥1 asthma exacerbation (risk ratio [RR] = 0.66, 95%CI = 0.45-0.98) compared to control. AERR of BT versus control was non-significant, but significant improvements in ACQ score (mean difference [MD] -0.41, 95%CI -0.63 to -0.20), AQLQ score (MD = 0.54, 95%CI = 0.30-0.77), amPEF and OCDR were found. No significant differences between BT and biologics were seen across indirect comparisons of all studies. CONCLUSIONS: Despite the lack of head-to-head comparative trials, this NMA suggests that BT is non-inferior to biologicals in terms of quality-of-life scores, and represents a promising alternative for patients with severe asthma.


Subject(s)
Asthma , Biological Products , Bronchial Thermoplasty , Humans , Biological Products/therapeutic use , Network Meta-Analysis , Asthma/drug therapy , Asthma/surgery , Adrenal Cortex Hormones/therapeutic use
19.
J Med Invest ; 70(1.2): 271-275, 2023.
Article in English | MEDLINE | ID: mdl-37164732

ABSTRACT

Despite the relatively short follow-up period in our previous study, we had reported that increased cough reflex sensitivity (CRS) may predict the efficacy of bronchial thermoplasty (BT) for treating asthma. Herein, we examined whether CRS predicts the efficacy of BT 2 years after the final BT treatment. We also investigated the influence of BT on CRS. We reviewed 10 patients 2 years after their final BT treatment. CRS, asthma-related symptoms, asthma exacerbations, and cough-related quality of life were assessed at baseline and 2 years after BT. Five patients responded positively to BT (BT responders) and their asthma control improved. No significant difference in CRS at baseline was detected between the BT responders and nonresponders. In contrast, BT responders exhibited significant improvements in CRS 2 years after BT. CRS at baseline could not predict the BT efficacy after 2 years. This is the first report demonstrating BT desensitized CRS in consecutive case series. J. Med. Invest. 70 : 271-275, February, 2023.


Subject(s)
Asthma , Bronchial Thermoplasty , Humans , Retrospective Studies , Follow-Up Studies , Cough , Quality of Life , Asthma/surgery , Reflex
20.
Curr Opin Pulm Med ; 29(1): 43-46, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36474463

ABSTRACT

PURPOSE OF REVIEW: Severe asthma is associated with frequent hospital visits and impact in quality of life as well as healthcare associated costs. Limited treatment modalities exist to assist in reduction of frequent exacerbations in patients with severe asthma who are already on maximum inhaler therapy. As supporting data becomes more robust, novel treatments have gained attention such as bronchial thermoplasty and immune-directed therapies. RECENT FINDINGS: Based on review of recent studies, bronchial thermoplasty poses itself as a potential intervention for severe asthma, demonstrating a decrease in asthma exacerbations with long term clinical effect and safety profile at the expense of temporary uncontrolled asthma symptoms for the first six weeks following the procedure. SUMMARY: In select patients with severe asthma, bronchial thermoplasty is a well tolerated and effective treatment to reduce asthma exacerbation.


Subject(s)
Bronchial Thermoplasty , Humans , Quality of Life
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