Use of MDCT to Assess the Results of Bronchial Thermoplasty.

OBJECTIVE: The purpose of this study was to evaluate the use of MDCT to assess response to bronchial thermoplasty treatment for severe persistent asthma. MATERIALS AND METHODS: MDCT data from 26 patients with severe persistent asthma who underwent imaging before and after bronchial thermoplasty were analyzed retrospectively. Changes in the following parameters were assessed: total lung volume, mean lung density, airway wall thickness, CT air trapping index (attenuation < -856 HU), and expiratory-inspiratory ratio of mean lung density (E/I index). Asthma Quality of Life Questionnaire score changes were also assessed. RESULTS: Median total lung volumes before and after bronchial thermoplasty were 2668 mL (range, 2226-3096 mL) and 2399 mL (range, 1964-2802 mL; p = 0.08), respectively. Patients also showed a pattern of obstruction improvement in air trapping values (median before thermoplasty, 14.25%; median after thermoplasty, 3.65%; p < 0.001] and in mean lung density values ± SD (before thermoplasty, -702 ± 72 HU; after thermoplasty, -655 ± 66 HU; p < 0.01). Median airway wall thickness also decreased after bronchial thermoplasty (before thermoplasty, 1.5 mm; after thermoplasty, 1.1 mm; p < 0.05). There was a mean Asthma Quality of Life Questionnaire overall score change of 1.00 ± 1.35 (p < 0.001), indicating asthma clinical improvement. CONCLUSION: Our study showed improvement in CT measurements after bronchial thermoplasty, along with Asthma Quality of Life Questionnaire score changes. Thus, MDCT could be useful for imaging evaluation of patients undergoing this treatment.

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

BACKGROUND: Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE: We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS: BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS: One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS: These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting ß2-agonists.

Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS).

Background: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin-13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard-of-care treatment. Methods: Adolescents (aged 12-17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%-90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks. Results: Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28-0.83]; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 [95% CI 0.35-1.03]; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/µl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 [95% CI 0.21-0.89]; 37.5 mg: 0.42 [95% CI 0.19-0.93]). Treatment-emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred. Conclusion: Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results. Clinical trial registration: NCT01875003 (www.ClinicalTrials.gov).

Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial.

RATIONALE: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. OBJECTIVES: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists. METHODS: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). MEASUREMENTS AND MAIN RESULTS: The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively). CONCLUSIONS: BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. METHODS: Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 µg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-ß2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT. RESULTS: 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. CONCLUSIONS: The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

Asthma control during the year after bronchial thermoplasty.

BACKGROUND: Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. METHODS: We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed. RESULTS: The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. CONCLUSIONS: Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].).

Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma.

RATIONALE: Bronchial thermoplasty (BT) is designed to reduce airway smooth muscle and improve asthma control. OBJECTIVES: This study was conducted to determine the safety and efficacy of this procedure in subjects with symptomatic, severe asthma. METHODS: Adults who were symptomatic despite treatment with fluticasone or equivalent at more than 750 mug/day, a long-acting beta(2)-agonist, and other medications, which could include 30 mg or less of oral prednisolone/day, were randomized to BT or to a control group. After treatment, subjects entered a 16-week steroid stable phase (Weeks 6-22), a 14-week steroid wean phase (Weeks 22-36), and a 16-week reduced steroid phase (Weeks 36-52). MEASUREMENTS AND MAIN RESULTS: BT resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred in 4 of 15 BT subjects during the treatment period. Five hospitalizations were within 3 days of treatment. Two subjects had segmental collapse involving the most recently treated lobe; one required bronchoscopy and aspiration of a mucus plug. There were no hospitalizations during this period in the 17 control subjects. The rate of hospitalizations was similar in both groups in the post-treatment period. At 22 weeks, BT subjects had significant improvements versus control subjects in rescue medication use (-26.6 +/- 40.1 vs. -1.5 +/- 11.7 puffs/7 d, P < 0.05), prebronchodilator FEV(1)% predicted (14.9 +/- 17.4 vs. -0.94 +/- 22.3%, P = 0.04), and Asthma Control Questionnaire scores (-1.04 +/- 1.03 vs. -0.13 +/- 1.00, P = 0.02). Improvements in rescue medication use and Asthma Control Questionnaire scores remained significantly different from those of controls at 52 weeks. CONCLUSIONS: BT is associated with a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 00214539).

Survival in idiopathic pulmonary fibrosis-cytotoxic agents compared to corticosteroids.

STUDY OBJECTIVE: To compare the survival of patients with IPF treated retrospectively with corticosteroids alone, to survival of patients treated with immunosuppressive and corticosteroids combined. DESIGN: Non-randomized retrospective cohort study. SETTING: Three tertiary centers in Brazil. PATIENTS: Eighty-two IPF patients were included. The diagnosis was confirmed by open lung biopsy in 48. Patients received either corticosteroids alone (group I) or cytotoxic agents in addition to corticosteroids (group II). MEASUREMENTS AND RESULTS: The primary end-point was mortality. Secondary outcome included longitudinal changes in FVC. Mean age was 66+/-8 years. FVC was 71+/-17% of predicted. There were 48 deaths during the study period (59%), 44 secondary to respiratory causes. From preliminary univariate analysis, for the group as a whole, worse survival was found to be associated with FVC% <70% of predicted (P=0.004), evidence of disease progression by follow-up FVC measurements (P=0.01), and pharmacologic treatment (P=0.014). Median survival was 25 months for the group I, and 45 months for the group II (Log-Rank=6.45, P=0.01). After adjusting for FVC > or =70% and<70% of predicted, there was evidence to indicate that survival was associated with recommended pharmacologic treatment only in patients with FVC> or =70% (Log Rank=6.84, P=0.009). CONCLUSIONS: The combination of immunosuppressive agents and prednisone results in better survival when compared to prednisone alone in patients with IPF. The benefit seems to occur only in patients with less severe disease, as reflected by FVC> or =70%.

Magnetic resonance of the lung: a step forward in the study of lung disease.

Magnetic resonance imaging (MRI) of the lung has progressed tremendously in recent years. Because of improvements in speed and image quality, MRI is now ready for routine clinical use. The main advantage of MRI of the lung is its unique combination of structural and functional assessment in a single imaging session. We review the three major clinical indications for MRI of the lung: staging of lung tumors; evaluation of pulmonary vascular disease; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation.

Ressonância magnética de pulmão: um novo passo no estudo das doenças pulmonares / Magnetic resonance of the lung: a step forward in the study of lung disease

A ressonância magnética (RM) de pulmão progrediu tremendamente nos últimos anos. Devido a melhorias na velocidade e na qualidade de imagens, a RM de pulmão hoje está pronta para a utilização clínica de rotina. A principal vantagem da RM de pulmão é a sua combinação exclusiva de avaliação estrutural e funcional em uma única sessão de imagens. Revisamos aqui as três principais indicações clínicas da RM de pulmão: o estadiamento de tumores pulmonares, a avaliação de doença vascular pulmonar e a investigação de anormalidades pulmonares em pacientes que não podem ser expostos à radiação.

Magnetic resonance imaging (MRI) of the lung has progressed tremendously in recent years. Because of improvements in speed and image quality, MRI is now ready for routine clinical use. The main advantage of MRI of the lung is its unique combination of structural and functional assessment in a single imaging session. We review the three major clinical indications for MRI of the lung: staging of lung tumors; evaluation of pulmonary vascular disease; and investigation of pulmonary abnormalities in patients who should not be exposed to radiation.

Doença broncopulmonar obstrutiva crônica (DBPOC): estudo de 255 pacientes (395 internaçöes) / Chronic obstructive pulmonary disease: study of 255 patients

Analisam-se os casos de 255 pacientes portadores de DBPOC (enfisema pulmonar e/ou bronquite crônica) que tiveram a primeira internaçäo no serviço no período 1977-1984; 219(86,0%) eram homens com média de idade de 60,7 anos. Havia 229 fumantes (89,40%) - em média 26,7 cigarros/dia, e durante 41 anos. Dos 255 pacientes, 187 (Grupo I) tiveram somente uma internaçäo no serviço, e 68 (Grupo II) hospitalizaram-se de duas a dez vezes, até o ano de 1987. A soma das primeiras internaçöes com as reinternaçöes totalizou 395 hospitalizaçöes. A causa mais comum desencadeante das internaçöes foi infecçäo respiratória (41,0%), ocorrendo especialmente durante o inverno ou início da primavera. Verificou-se o padräo "enfisematoso" da DBPOC em 32,5% dos pacientes, o "bronquítico" em 10,0% e 57,5% eram casos "mistos". Tosse, expectoraçäo e dispnéia foram os sintomas mais freqüentes (em torno de 85,0%); sibilância ocorreu em 47,5% dos pacientes, e em 12,0% cianose. Evidências de insuficiência cardíaca, esquerda associada a DBPOC foram detectadas em 50 pacientes (19,6%), e 28(11,0%) tinham "cor pulmonale". O VEF1 foi inferior a 1,2 litros em 58,0% dos pacientes, já na primeira internaçäo. Metade dos pacientes tinha PaO2 abaixo de 60 mmHg (um terço dos quais com hipercapnia). Achado radiográfico sugestivo de pneumonia esteve presente em 57,5% dos pacientes na primeira internaçäo, e em 34,0% das reinternaçöes. Oito pacientes (3,0%) tiveram pneumotórax. Pneumococo e/ou Haemophoilus influenzae foram encontrados na escarro de 88,5% dos pacientes infectados. Todos os pacientes receberam tratamento clínico, e sete também cirúrgico (drenagem de pneumotórax, em geral)...