Patients with severe persistent asthma experience significant morbidity and higher mortality. To the authors knowledge, this is a first report examining the effects of bronchial thermoplasty one year post procedure completion in a patient population with obesity.
Of the 18 patients who had improved with bronchial thermoplasty, 14 were on chronic oral corticosteroids of which 2 were able to be weaned down and 10 patients in total completely off their chronic oral corticosteroids. In the Research in Severe Asthma (RISA) Trial, a controlled safety study in which 32 severe asthma patients (15 receiving BT and 17 with continued usual care) where undergone forced steroid withdrawal (5), demonstrated that the BT group demonstrated improved asthma control and reduced use of rescue medications prior to forced withdrawal and continued to show reduced short-acting bronchodilator usage, more symptom-free days and improved ACQ scores. The use of OCS and ICS fell by 63.5% and 28.6% in the BT group compared to 26.2% and 20% in the control usual care group (5). Comparing BT to Mepolizumab over a 12-month period, one study showed improvement but no differences between the two modalities for ACQ score, exacerbation rate, reduction in reliever use or oral corticosteroids (-3.3 ± 7.5 vs - 5.8 ± 6.7 mg/day) (6). In another study comparing 199 patients who were treated with omalizumab, mepolizumab, benralizumab or BT and to evaluate the efficacy of these treatments over a 12-month observation period, all agents resulted in statistically significant reduction in hospitalizations and reduction of exacerbations; however, the best OCS sparing effect was obtained by BT (- 76%, p < 0.0001) and mepolizumab (- 90.2%, p = 0.002) compared Omalizumab and Benralizumab (7). In our study, although small sample size, 8/18 improved patients were on biological agents pre-BT (2 on Benralizumab, 1 on Mepolizumab, 1 on Omalizumab, 1 on Reslizumab, 2 on Dupilumab and 1 on Omalizumab with Benralizumab), of whom all 6/8 patients on both a biologic and chronic OCS were completely titrated off their OCS following BT therapy, in addition to one patient not on chronic OCS was weaned off their inhaled corticosteroid dose. Compared to biologics, BT may have a comparable effect in improving severe refractory asthma, however an observation in our severe patient population was showing that BT consistently reduced OCS by average 10.7 mg (p<0.002). If symptoms remain persistent while on biologics, BT addition may add further asthma control and reduction of OCS as seen in our study of 10.1 mg (p<0.02) reduction in BT patients previously on biologics.
Of the patients who had improvement following the BT procedure, 16/18 (89%) were effectively able to be weaned off some portion of their chronic regimen. Weight loss may help obese patients obtain better control of their asthma. As increased airways resistance and closing of bronchioles can lead to asthma related symptoms, weight loss can improve mechanics such as chest wall offloading or positive pressure ventilation to limit bronchiole closure helping to relieve symptoms (8). In a 2015 study by Parkhale et al. a study involving 22 asthmatics with a BMI > 32.5 kg/m2, weight loss resulted in an improvement in airway hyperreactivity, asthma control, lung function, and quality of life (9); while a more recent 2017 study also showed reduction in inflammatory markers (10). A 2019 systematic review involving four trials (246 children and 502 adults) concluded that weight loss from any measure (dietary restrictions, exercise or behavioral therapy) generally resulted in improved asthma control and quality of life (11). A 2015 study of 330 severely obese adults (BMI avg 37.5 kg/m2) found that a weight loss of >10% was required to produce meaningful improvement in asthma (12). In our study, weight loss of average 6.4 kg was a significant outcome, this could be possibly explained from a couple different stand points. First those patients with the most weight loss also were on higher doses of chronic corticosteroids pre procedure or were able to come off the corticosteroids entirely following completion of bronchial thermoplasty. In addition, there may have been an effect of increased mobility in these patients as they would be able to accomplish more with their activities of daily living without being inhibited as much with their asthmatic symptoms.
Another explanation of why BT may work in an obese population is the improvement potentially offered by improving airways resistance. In a 1993 study performed by Zerah et al, respiratory and airway resistance was determined of 46 individuals at three different stages of obesity and significant negative correlations with BMI were found (13). The authors of this study reported a significant correlation between airway conductance and functional reserve capacity in their study which suggest that low lung volume is crucial in determining the increase in resistance and previous studies by Briscoe had shown that airway conductance was linearly related to lung volumes (13–14). Along with a decrease in expiratory flow rates with a preserved FEV1/FVC ratio, the authors concluded that in obesity, airway abnormalities involved increase in proximal airways resistance rather than distal airways; an increase in respiratory resistance and airway resistance that was significant with the level of obesity that was related due to the decrease in lung volumes (13). In a study by Langton et al. utilizing body plethysmography, following BT treatment, they were able to show a significant 9% reduction in residual volume and 21% reduction in airway resistance along with a 34% increase in airway conductance (15). Donovan et al. recently used human lung specimens to further describe the effects of BT. Using bronchial thermoplasty to cause a 75% reduction in airway smooth muscles, they were able to show a global redistribution of flow to the treated central airways leaning to reopening of small airways and improvement in lung function and flow patterns (16). This may help explain why in this obese population who are treated with BT, there is a clinical improvement in asthma without an improvement in spirometry values as was seen in our study in addition to previous studies demonstrated in the AIR2 trial and PAS2 study (3, 4). As increasing obesity may disrupt airways resistance and flow patterns, BT may lead to alterations causing more homogenous flow patterns which can reduce airway resistance and improve ventilation.
Although baseline weight or BMI is not reported, one observational study of 194 patients by Thomas et al. showed that the use of Mepolizumab had a significant reduction in mean oral corticosteroid dose and patient weight in those associated with positive clinical response 6 months following treatment initiation (17). Data on biological agents and weight loss is overall limited, further studies need to be conducted however BT may be of consideration sooner in obese patients who fail to show benefit from biological agents.
The post-procedure hospitalization rate for asthma exacerbations was higher than previously reported during the PAS2 and AIR2 studies at 43% compared to 13.2% vs 8.4% respectively (3, 4). Although our hospitalization rates were significantly higher, with a small sample size the value may not be as statistically significant in comparison to the previous larger studies. Nonetheless, patients who were hospitalized for asthma exacerbations did not have prolonged or complicated hospitalizations courses and over a 12-month period still received significant benefits from the BT procedure in relation to their asthma control.
The limitations of this study did revolve around the retrospective design. The groups of comparison were those patients with documented benefit from the procedure versus those who did not show significant improvement. With the retrospective design we were able to criticize those three of the five patients who may have been mis-diagnosed with severe asthma and had other uncontrolled etiologies to give them asthma-like symptoms. One patient who was later diagnosed with vocal cord dysfunction did have a suspicion prior to the therapy and was evaluated by Otolaryngology and was determined prior to the procedure that her symptoms were likely asthma related. Following the third procedure the patient required to be re-intubated for significant dyspnea and her diagnosis of VCD was confirmed at that time with direct laryngoscopy and improvement of stridor immediately following endotracheal intubation. Other limitations consisted of retrospective review of charts to determine how the patients best received benefit post BT and their exact asthma quality of life questionnaire (AQLQ) scoring was not able to be quantified.
In conclusion, bronchial thermoplasty may be a beneficial modality for obese patients with uncontrolled asthma in helping to reduce among of oral corticosteroids dependence, decrease in exacerbations faced and was associated with a significant reduction in weight loss 12 months post procedure. The procedure may be offered to this patient population with an anticipated increased rate of post-procedure exacerbation hospitalization.