Loss of bronchoprotection to Salbutamol during sputum induction with hypertonic saline: implications for asthma therapy

Juan Carlos Ivancevich Friday, 11 May 2018 13:50
Hongyu WangMelanie KjarsgaardTerence HoJohn D. Brannan and Parameswaran Nair

Abstract

Background

Sputum induction with hypertonic saline in obstructive airway diseases is generally safe. However, saline induces bronchoconstriction in some patients despite pre-medication with Salbutamol. Our objectives were to investigate the predictors of failure of Salbutamol to protect against saline-induced-bronchoconstriction in patients with asthma and COPD and to evaluate implications for asthma therapy.

Methods

Retrospective survey on a database of 3565 patients with obstructive airway diseases who had sputum induced with hypertonic saline. The effect of baseline FEV1, bronchitis and concomitant medication on saline-induced-bronchoconstriction (≥ 15% drop in FEV1) were examined by logistic regression analysis. A subgroup had this re-examined 8–12 weeks after decreasing long-acting-beta-2-agonist dose or after adding Montelukast, which included an assessment of mast cell activity in sputum.

Results

222 (6.2%) patients had saline-induced-bronchoconstriction despite pre-treatment with inhaled Salbutamol. Baseline airflow obstruction (FEV1% predicted < 60% OR 3.29, p < 0.001) and long-acting-beta-agonist use (OR 2.02, p = 0.001), but not bronchitis, were predictors of saline-induced-bronchoconstriction, which decreased when long-acting-beta-agonist dose was decreased. Refractoriness to subsequent bronchodilation was associated with mast cell activity and was attenuated by Montelukast.

Conclusion

Sputum induction with saline provides information on bronchitis and additional physiological data on tolerance to beta-agonists and mast cell activity that may have implications for clinical therapy.

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Role of Immunotherapy in the Treatment of Asthma

Juan Carlos Ivancevich Saturday, 28 April 2018 20:07

SYSTEMATIC REVIEW

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These reports are available in PDF only (Full Report [3.0 MB]; Evidence Summary [370 KB]). People using assistive technology may not be able to fully access information in these files. For additional assistance, please contact us.

Key Messages

Purpose of Review

To assess the efficacy and safety of immunotherapy for treating allergic asthma.

Key Messages

  • Subcutaneous immunotherapy reduces use of long-term control medications. It may also improve quality of life and FEV1, (a measure of the ability to exhale) and reduce the use of quick-relief medications (short-acting bronchodilators) and systemic corticosteroids.
  • Sublingual immunotherapy improves asthma symptoms, quality of life and FEV1, and reduces the use of long-term control medications. It may also reduce the use of quick-relief medications.
  • Local and systemic reactions to subcutaneous immunotherapy and sublingual immunotherapy are common but infrequently required changes in treatment. Life-threatening events (such as anaphylaxis) are reported rarely.

Structured Abstract

Objectives. To evaluate the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in the treatment of allergic asthma.

Data Sources. We searched PubMed, Embase, and CENTRAL through May 8, 2017.

Methods. Two reviewers independently selected randomized controlled trials (RCTs) of the efficacy of SCIT and SLIT and RCTs, observational studies, and case series or case reports on safety. Two reviewers independently assessed the risk of bias for each study and together graded the strength of the evidence.

Results. We identified 54 RCTs on efficacy: 31 assessed SCIT and 18 assessed SLIT and 5 on SCIT versus SLIT. We included 80 studies on safety: 26 RCTs and 18 non-RCTs for SCIT, 20 RCTs and 10 non-RCTs for SLIT and one non-RCT on SCIT versus SLIT.

SCIT reduces the use of long-term control medications [moderate strength of evidence (SOE)]. SCIT may improve quality of life, reduce the use of quick-relief medications (short-acting bronchodilators), reduce the need for systemic corticosteroids, and improve FEV1 (low SOE). There was insufficient evidence regarding the effect of SCIT on asthma symptoms and health care utilization. Local and systemic allergic reactions were frequent but infrequently required a change in treatment. We are unable to draw conclusions about whether SCIT increased risk of anaphylaxis, primarily because anaphylaxis was not directly measured (insufficient SOE). There was one case report of a death determined possibly to be caused by SCIT.

SLIT improves asthma symptoms (high SOE); decreases use of long-term control medication and improves FEV1 (moderate SOE). SLIT may decrease quick-relief medication use, and may improve quality of life (low SOE). There was insufficient evidence about the effect of SLIT on systemic corticosteroid use and health care utilization. Local and systemic allergic reactions were common but infrequently required changes in treatment. Life-threatening reactions were not commonly reported, with three case reports of anaphylaxis (insufficient SOE) and no deaths (moderate SOE) reported.

There was insufficient evidence to draw conclusions about the comparative effects of SCIT versus SLIT or for differential effects of immunotherapy based on patient age, setting of administration, or type of allergen.

Conclusions. Overall, SLIT and SCIT were beneficial for the majority of asthma-related outcomes assessed in this report. Local and systemic allergic reactions were common but infrequently required changes in treatment. Life-threatening events (such as anaphylaxis) were reported rarely.

Journal Publication

Rice JL, Diette GB, Suarez-Cuervo C, Brigham E, Lin SY, Ramanathan, Jr., M, Robinson KA, Azar A. Allergen-Specific Immunotherapy in the Treatment of Pediatric Asthma:  A Systematic Review[link is external]. Pediatrics. 2018 March 23 [epub ahead of print]. (doi: 10.1542/peds.2017-3833)

Citation

Suggested citation: Lin SY, Azar A, Suarez-Cuervo C, Diette GB, Brigham E, Rice J, Ramanathan M, Gayleard J, Robinson KA. The Role of Immunotherapy in the Treatment of Asthma. Comparative Effectiveness Review No. 196 (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No.290-2015-00006-I). AHRQ Publication No. 17(18)-EHC029-EF. Rockville, MD: Agency for Healthcare Research and Quality. March 2018. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER196[link is external].

The course of asthma during pregnancy in a recent, multicase–control study on respiratory health

Juan Carlos Ivancevich Friday, 20 April 2018 14:30
A. Grosso, F. LocatelliE. GiniF. AlbiciniC. TirelliI. Cerveri and A. G. Corsico

Abstract

Background

Over the years it has been widely stated that approximately one-third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced.

Methods

A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study.

Results

Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years ± 1.4), unlike the other women who started to use ICS much later (30.3 years ± 12). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years ± 9 vs 13 years ± 10). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20.

Conclusion

Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnancy.

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Severe, eosinophilic asthma in primary care in Canada: a longitudinal study of the clinical burden and economic impact based on linked electronic medical record data

Juan Carlos Ivancevich Friday, 27 April 2018 12:46
Don Husereau, Jason GoodfieldRichard LeighRichard BorrelliMichel Cloutier and Alain Gendron

Abstract

Background

Stratification of patients with severe asthma by blood eosinophil counts predicts responders to anti-interleukin (IL)-5 (mepolizumab and reslizumab) and anti-IL-5 receptor α (benralizumab) therapies. This study characterized patients with severe asthma who could qualify for these biologics in a primary care setting.

Methods

We retrospectively selected patients from July 1, 2010, to June 30, 2014, using a linked electronic medical records (EMR) database (IMS Evidence 360 EMR Canada) for > 950,000 patients in primary care in Ontario, Canada. Patients aged ≥ 12 years with ≥ 2 documented asthma diagnoses were identified as having severe asthma based on prescriptions for high-dosage inhaled corticosteroids (ICS) plus either a leukotriene receptor antagonist, long-acting β2-agonist (LABA), or theophylline filled on the same day. Patients’ asthma was considered severe also if they received a prescription for ICS with oral corticosteroids (OCS) or an additional prescription for omalizumab. Patient characteristics, asthma-related medications, and blood eosinophil counts were captured using observed care patterns for the year prior to ICS/LABA and/or OCS prescription. Health care resource use (HCRU) and costs were captured throughout the 1-year follow-up period.

Results

We identified 212 patients who met the criteria for severe asthma. These patients required an average of 6.5 physician visits during the 1-year follow-up period (95% confidence interval 5.7–7.3), and 20 (9%) were referred to respiratory specialists. Overall, 56 patients (26%) with severe asthma had complete blood counts, of whom 23 (41%) had blood eosinophil counts ≥ 300 cells/μL and might be considered for anti-eosinophil therapies. Patients with severe asthma and blood eosinophil counts ≥ 300 cells/μL had more respiratory specialist referrals (17% vs. 12%) than patients with blood eosinophils < 300 cells/μL.

Conclusions

Our data suggest that during 2010–2014, Ontario primary care patients with severe asthma and high blood eosinophil counts had greater HRCU than those with lower counts. Approximately 41% of patients with severe asthma could qualify for anti-eosinophil drugs based on blood eosinophil counts. However, the eosinophilic status of most patients was unknown. It is appropriate to increase awareness of the use of blood eosinophil counts to identify patients who could be considered for anti-eosinophil therapies.

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Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma

Juan Carlos Ivancevich Wednesday, 18 April 2018 11:36
BMC Pulmonary Medicine
BMC series – open, inclusive and trusted 2018 18:29
 
N. Facciolongo, A. DiStefanoV. PietriniC. GaleoneF. BellanovaF. MenzellaN. ScichiloneR. PiroG. L. BajocchiB. BalbiL. AgostiniP. P. SalsiD. Formisano and M. Lusuardi

Abstract

Background

Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year.

Methods

Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, exacerbations, hospitalizations, oral corticosteroids use were also collected at the same time points.

Results

A statistically significant reduction at T1, T2 and T12 of nerve fibers was observed in the submucosa and in ASM compared to T0. Among inflammatory cells, only CD68 showed significant changes at all time points. Improvement of all clinical outcomes was documented and persisted at the end of follow up.

Conclusions

A reduction of nerve fibers in epithelium and in ASM occurs earlier and persists at one year after BT. We propose that nerve ablation may contribute to mediate the beneficial effects of BT in severe asthma.

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Editor: Juan C. Ivancevich, MD

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