AABIP IP Fellow Reading List

Asthma and Other COPD Treatments

New bronchoscopic treatment modalities for patients with chronic bronchitis

https://pubmed.ncbi.nlm.nih.gov/33472961/

Review

Reference: Hartman JE, Garner JL, Shah PL, Slebos DJ. New bronchoscopic treatment modalities for patients with chronic bronchitis. Eur Respir Rev. 2021;30(159):200281.

Summary: 

Chronic bronchitis is a progressive disease that is  often difficult to treat. This article reviews new bronchoscopic treatments for this disease that are currently under investigation.

Liquid nitrogen metered cryospray, bronchial rheoplasty and balloon desobstruction have the intent of destroying hyperplastic goblet cells and excess submucousal glands. These therapies are in an early phase of clinical research and larger randomized controlled trials are needed to confirm the pilot data available and to evaluate the treatment durability.

Targeted lung denervation (TLD) is the ablation of parasympathetic nerves that run along mainstem bronchi to decrease release of acetylcholine, which regulates smooth muscle tone. This modality is at a more advanced stage and promising effects on exacerbation frequency have been shown, however, confirmation of the benefit in improvement in chronic bronchitis symptoms is still needed.

Safety of delivering bronchial thermoplasty in two treatment sessions

https://pubmed.ncbi.nlm.nih.gov/34844622/

Clinical Trial

Reference: Koshy K, Sha J, Bennetts K, Langton D. Safety of delivering bronchial thermoplasty in two treatment sessions. Respir Res. 2021;22(1):307.

Background: This is a prospective observational study evaluating the safety of compressing bronchial thermoplasty into two treatment sessions compared with the traditional 3 treatment approach.

PICO:
Population:
  • Severe asthma patients
Intervention:
  • Two BT sessions, one for whole left lung and one for right lung 4 weeks later. This was considered an accelerated treatment schedule (ABT) (n = 16)
Comparison: 
  • Conventional BT scheduling (CBT), three session treatments (n = 37)
Outcome:
  • Safety:
    • Requirement to remain in hospital beyond the electively planned 24-h admission (27.9% with ABT vs 5.4% with CBT; p = 0.0025)
    • ICU monitoring required in 16.1% ABT and 0.9% of CBT (p = 0.002)
    • Need for re-admission for any cause within of 30 days of treatment was similar, 6.4% vs 5.4%
  • Similar number of radiofrequency activations between ABT and CBT

Take home: ABT associated with greater short-term deterioration in lung function associated with greater risk of prolonged hospitalization due to wheezing and which predominantly affected females and ICU monitoring. No statistically significant difference in 30-day hospital readmission.

Bronchial thermoplasty in patients with severe asthma at 5 years: the post-fda approval clinical trial evaluating bronchial thermoplasty in severe persistent asthma study

https://pubmed.ncbi.nlm.nih.gov/34774528/

Clinical Trial

Reference: Chupp G, Kline JN, Khatri SB, et al. Bronchial thermoplasty in patients with severe asthma at 5 years: the post-fda approval clinical trial evaluating bronchial thermoplasty in severe persistent asthma study. Chest. 2022;161(3):614-628.

Background: Prospective, open-label, observational, multicenter study. This study is the Post-FDA BT Approval Clinical Trial Evaluating Bronchial Thermoplasty (BT) in Severe Persistent Asthma (PAS2) study which collected data on patients with severe asthma undergoing this procedure.

PICO:

Population:

  • Severe asthma patients age 18-65 on inhaled corticosteroid and long acting beta-agonist (n = 227)
  • Spirometry was evaluated at baseline and at years 1 through 5 post-treatment.

Intervention:

  • None

Comparison:

  • Evaluation of severe exacerbations, hospitalization, ED visits, and medication usage in same patients 12 months prior to BT and at years 1 through 5

Outcome:

  • Five years after treatment, patients experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure

Take home: Bronchial thermoplasty improves severe exacerbations, hospitalizations, ED visits and corticosteroid exposure across different asthma phenotypes. This improvement in control persists at least 5 years post treatment.

A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD

https://pubmed.ncbi.nlm.nih.gov/32586881/

Clinical Trial 

Reference: Garner JL, Shaipanich T, Hartman JE, et al. A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD. Eur Respir J. 2020;56(6):2000556.

Background: The objective of this study was to evaluate the feasibility, efficacy and safety of metered cryospray (MCS) for management of chronic bronchitis.

PICO:

Population –

  • Patients age 47-76 with a FEV1 of 30–80% predicted who were medically optimized and had quit smoking >2 months prior to enrollment (n =35)

Intervention –

  • 35 patients underwent staggered liquid nitrogen treatments to the tracheobronchial tree
  • 34 patients completed three treatments, each lasting 34.3 ± 12.1 minutes, separated by 4–6 weeks
    • 1st right lower lobe and mainstem; 2nd left lower lobe and mainstem; 3rd upper lobes and trachea
    • On average 17.3, 17.6 and 26.2 sprays for treatments 1, 2 and 3 respectively

Comparison –

  • None

Outcome –

  • Clinically meaningful improvements in patient-reported outcomes (SGRQ, CAT and LCQ) were observed at 3 months, 6 months and 9 months
  • Patients with SGRQ >50 (poorer baseline health status) had greatest benefits which persisted at 12 months

Take home: MCS is safe, feasible and associated with clinically meaningful improvements in multidimensional patient-reported outcomes.

Bronchial rheoplasty for treatment of chronic bronchitis. Twelve-month results from a multicenter clinical trial

https://pubmed.ncbi.nlm.nih.gov/32407638/

Clinical Trial 

Reference: Valipour A, Fernandez-Bussy S, Ing AJ, et al. Bronchial rheoplasty for treatment of chronic bronchitis. Twelve-month results from a multicenter clinical trial. Am J Respir Crit Care Med. 2020;202(5):681-689.

Background: Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. The study evaluated the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with chronic bronchitis.

PICO:

Population –
  • Patients at least 40 years old with at least 10 pack year smoking history with clinical chronic bronchitis (n = 30)
Intervention –
  • Bilateral bronchial rheoplasty applied and follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and St. George's Respiratory Questionnaire (SGRQ)
Comparison –
  • None
Outcome –
  • The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. No events in 12 months follow up.
  • 30% rate of nonserious, moderate COPD exacerbations during treatment recovery period
  • Histologically, the mean goblet cell hyperplasia score after treatment was relatively reduced by 39% (p < 0.001)
  • Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; p = 0.0002) and SGRQ (mean, -14.6; median, -7.2; p = 0.0002) scores were observed, with similar observations through 12 months

Take home: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with chronic bronchitis.

Follow-up outcomes of chronic obstructive pulmonary disease patients who underwent dilatation and curettage with the Karakoca resector balloon: A 188-case series over 5 years

https://pubmed.ncbi.nlm.nih.gov/30508939/

Clinical Trial

Reference: Karakoca Y, Gogus G, Akduman S, Erturk B. Follow-up outcomes of chronic obstructive pulmonary disease patients who underwent dilatation and curettage with the Karakoca resector balloon: A 188-case series over 5 years. Medicine (Baltimore). 2018;97(48):e13400.

Background: Patients with GOLD stage III and IV COPD with no symptomatic relief from optimized medical management underwent Karakoca resector balloon dilatation and curettage technique for segmental and subsegmental bronchi by therapeutic bronchoscopy with the goal of compressing hyperplasic goblet cells.

PICO:

Population –

  • Patients with GOLD stage III and IV COPD and chronic bronchitis predominant on PFT, high resolution CT and/or quantitative ventilation and perfusion scintigraphy (n = 188)

Intervention –

  • Karakoca resector balloon dilatation and curettage technique for segmental and subsegmental bronchi by therapeutic bronchoscopy with follow up in 1 week and one month

Comparison –

  • None

Outcome –

  • Statistically significant Improvement of (FEV1), oxygen saturation (SpO2), 6MWT and modified Borg dyspnea scale (MBS) (p < 0.001 each)
  • Improvement maintained for entire post procedure month with all but 4 male patients free of symptoms

Take home: Balloon dilatation and curettage is a safe, repeatable and successful technique for medical treatment-resistant stage III/IV COPD. Additional multicenter, larger scale and controlled studies are needed to provide evidence of efficacy and safety.

Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

https://pubmed.ncbi.nlm.nih.gov/33608007/

Clinical Trial

Reference: Pison C, Shah PL, Slebos DJ, et al. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes. Respir Res. 2021;22(1):62.

Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung, thus reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.

PICO:

Population –

  • Patients with moderate-to-severe, symptomatic COPD (n = 34)

Intervention –

  • Three year follow up for patients who received TLD

Comparison –

  • None

Outcome –

  • The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study
  • Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up
  • No new gastrointestinal adverse events and no unexpected serious adverse events were observed

Take home: TLD in COPD patients demonstrated a positive safety profile out to 3 years with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Two-year outcomes for the double-blind, randomized, sham-controlled study of targeted lung denervation in patients with moderate to severe copd: airflow-2

https://pubmed.ncbi.nlm.nih.gov/33177818/

Clinical Trial

Reference: Valipour A, Shah PL, Herth FJ, et al. Two-year outcomes for the double-blind, randomized, sham-controlled study of targeted lung denervation in patients with moderate to severe copd: airflow-2. Int J Chron Obstruct Pulmon Dis. 2020;15:2807-2816.

Background: Targeted lung denervation (TLD) disrupts parasympathetic pulmonary innervation of the lung and reduces clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability,  safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.

PICO:

Population –

  • COPD patients (FEV1 30-60% predicted, CAT≥10 or mMRC≥2) (n = 82)

Intervention –

  • TLD by using a novel lung denervation system (Nuvaira, Inc., USA) (n = 41)

Comparison –

  • 1:1 randomized, sham-controlled, double-blinded multicenter study (n = 41)
  • Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD

Outcome –

  • Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p = 0.04, HR = 0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p = 0.18, HR = 0.71)
  • No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups

Take home: TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Lung function and quality of life remained stable following TLD.