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Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis

Author/s: 
Bhatta, DN, Glantz, SA

INTRODUCTION:

E-cigarettes deliver an aerosol of nicotine by heating a liquid and are promoted as an alternative to combustible tobacco. This study determines the longitudinal associations between e-cigarette use and respiratory disease controlling for combustible tobacco use.

METHODS:

This was a longitudinal analysis of the adult Population Assessment of Tobacco and Health Waves 1, 2, and 3. Multivariable logistic regression was performed to determine the associations between e-cigarette use and respiratory disease, controlling for combustible tobacco smoking, demographic, and clinical variables. Data were collected in 2013-2016 and analyzed in 2018-2019.

RESULTS:

Among people who did not report respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma) at Wave 1, the longitudinal analysis revealed statistically significant associations between former e-cigarette use (AOR=1.31, 95% CI=1.07, 1.60) and current e-cigarette use (AOR=1.29, 95% CI=1.03, 1.61) at Wave 1 and having incident respiratory disease at Waves 2 or 3, controlling for combustible tobacco smoking, demographic, and clinical variables. Current combustible tobacco smoking (AOR=2.56, 95% CI=1.92, 3.41) was also significantly associated with having respiratory disease at Waves 2 or 3. Odds of developing respiratory disease for a current dual user (e-cigarette and all combustible tobacco) were 3.30 compared with a never smoker who never used e-cigarettes. Analysis controlling for cigarette smoking alone yielded similar results.

CONCLUSIONS:

Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking. Dual use, the most common use pattern, is riskier than using either product alone.

Keywords 
e-cigarette or vaping product use-associated lung injury vaping e-cigarettes smoking lung injury tobacco copd respiratory disease

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Author/s: 
Wechsler, ME, Szefler, SJ, Ortega, VE, Pongracic, JA, Chinchili, V, Lima, JJ, Krishnan, JA, Kunselman, SJ, Mauger, D, Bleecker, ER, Bacharier, LB, Beigelman, A, Benson, M, Blake, KV, Cabana, MD, Cardet, JC, Castro, M, Chmiel, JF, Covar, R, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Grossman, N, Holguin, F, Jackson, DJ, Kumar, H, Kraft, M, LaForce, CF, Lang, J, Lazarus, SC, Lemanske, RF Jr, Long, D, Lugogo, N, Martinez, F, Meyers, DA, Moore, WC, Moy, J, Naureckas, E, Olin, JT, Peters, SP, Phipatanakul, W, Que, L, Raissy, H, Robison, RG, Ross, K, Sheehan, W, Smith, LJ, Solway, J, Sorkness, CA, Sullivan-Vedder, L, Wenzel, S, Israel, E, NHLBI AsthmaNet

BACKGROUND:

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS:

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS:

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS:

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Keywords 
asthma African Americans glucocorticoids randomized control trial

Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma

Author/s: 
Beasley, Richard, Holliday, Mark, Reddel, Helen K., Braithwaite, Irene, Ebmeier, Stefan, Hancox, Robert J., Harrison, Tim, Houghton, Claire, Oldfield, Karen, Papi, Alberto, Pavord, Ian D., Williams, Mathew, Weatherall, Mark

BACKGROUND:

In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. The availability of data from clinical trials designed to better reflect clinical practice would be beneficial.

METHODS:

We conducted a 52-week, randomized, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients were randomly assigned to one of three treatment groups: albuterol (100 μg, two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms) (albuterol group); budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group); or budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide-formoterol group). Electronic monitoring of inhalers was used to measure medication use. The primary outcome was the annualized rate of asthma exacerbations.

RESULTS:

The analysis included 668 of 675 patients who underwent randomization. The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49; 95% confidence interval [CI], 0.33 to 0.72; P<0.001) and did not differ significantly from the rate in the budesonide maintenance group (absolute rate, 0.195 in the budesonide-formoterol group vs. 0.175 in the budesonide maintenance group; relative rate, 1.12; 95% CI, 0.70 to 1.79; P = 0.65). The number of severe exacerbations was lower in the budesonide-formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.

CONCLUSIONS:

In an open-label trial involving adults with mild asthma, budesonide-formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations. (Funded by AstraZeneca and the Health Research Council of New Zealand; Novel START Australian New Zealand Clinical Trials Registry number, ACTRN12615000999538.).

Keywords 
asthma randomized control trial

Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Author/s: 
Maricoto, Tiago, Monteiro, Luís, Gama, Jorge M. R., Correia-de-Sousa, Jamie, Taborda-Barata, Luís

Objectives

To evaluate the effect of inhaler education programs on clinical outcomes and exacerbation rates in older adults with asthma or chronic obstructive pulmonary disease (COPD).

Design

Systematic review and meta‐analysis.

Setting and Participants

Older adults with asthma or COPD, either in primary or secondary health care and pharmacy setting.

Measurements

We searched the Medline, Embase, and Central databases according to the main eligibility criteria for inclusion: systematic reviews, meta‐analysis, clinical trials and quasi‐experimental studies; participants aged 65 and older; education on inhaler technique and reporting of disease control and exacerbation rates. We used the Grading of Recommendations, Assessment, Development and Evaluations scale for quality assessment and used a random‐effect model with Mantel–Haenszel adjustment to perform a meta‐analysis.

Results

We included 8 studies (4 randomized, 4 quasi‐experimental) with a total of 1,812 participants. The most frequent type of intervention was physical demonstration of inhaler technique, training with placebo devices. Five studies showed significant reduction in exacerbation rates (pooled risk ratio=0.71, 95% confidence interval=0.59–0.86; p < .001), although effect on disease control and quality of life showed high discrepancy in the reported results, and all randomized studies revealed uncertainty in their risk of bias assessment.

Conclusion

All interventions seemed to improve inhaler performance and clinically relevant outcomes, but a placebo device could be the most effective. There is evidence that interventions reduce exacerbation risk in older adults, although to an overall moderate degree.

Keywords 
chronic obstructive pulmonary disease patient education inhalers asthma

Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma

Author/s: 
Sobieraj, Diana M., Baker, William L., Weeda, Erin R., Nguyen, Elaine, Coleman, Craig I., White, C. Michael, Lazarus, Stephen C., Blake, Kathryn V., Lang, Jason E.

Objective. To assess efficacy of intermittent inhaled corticosteroid (ICS) therapy in different populations (0 to 4 years old with recurrent wheezing, 5 years and older with persistent asthma, with or without long-acting beta agonist [LABA]), and to assess efficacy of added long-acting muscarinic antagonist (LAMA) in patients 12 years and older with uncontrolled, persistent asthma.

Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform.

Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use.

Results. We included 56 unique studies (54 randomized controlled trials, 2 observational studies) in this review. Compared to rescue short-acting beta-agonist (SABA) use, adding intermittent ICS reduces the risk of exacerbation requiring oral steroids and improves caregiver quality of life in children less than 5 years old with recurrent wheezing in the setting of a respiratory tract infection (RTI). In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence, leading to primarily low strength of evidence ratings. Using ICS and LABA as both a controller and quick relief therapy reduced the risk of exacerbations and improved symptom control in patients 12 years and older compared to ICS controller (with or without LABA). Data in patients 4 to 11 years old suggest lower risk of exacerbations with ICS and LABA controller and quick relief use, but with a lower strength of evidence than in the older population. In patients 12 years and older with uncontrolled, persistent asthma, LAMA versus placebo as add-on to ICS reduces the risk of exacerbations requiring systemic corticosteroids and improves lung function measure through spirometry. Current evidence does not suggest that a difference exists in the efficacy of LAMA versus LABA as add-on to ICS. Triple therapy of ICS, LAMA, and LABA improves lung function measured through spirometry, although the risk of exacerbation was not different versus ICS and LABA.

Conclusions. Intermittent ICS added to SABA during an RTI provides benefit to patients less than 5 years of age with recurrent wheezing. In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence for this question. In patients 12 years and older with persistent asthma, using ICS and LABA as both a controller and quick relief therapy may be more effective at preventing exacerbations than ICS controller (with or without LABA). LAMA is effective in the management of uncontrolled, persistent asthma in patients 12 years of age and older, and current evidence does not suggest a difference between LAMA and LABA as add-on to ICS.

Keywords 
asthma musacarinic antagonist corticosteroids

The Role of Immunotherapy in the Treatment of Asthma

Author/s: 
Lin, Sandra Y., Azar, Antoine, Suarez-Cuervo, Catalina, Diette, Gregory B., Brigham, Emily, Rice, Jessica, Ramanathan, Murugappan Jr., Gayleard, Jessica, Robinson, Karen A.

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.

Keywords 
asthma SLIT SCIT subcutaneous immunotherapy sublingual immunotherapy
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