Category: Featured Stories and Interviews

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Asthma and Exercise Feasibility

Asthma and Exercise Feasibility: A Randomized Pilot Study

Abstract

Background

Aerobic exercise appears to have clinical benefits for many asthmatics, yet a complete understanding of the mechanisms underlying these benefits has not been elucidated at this time.

Purpose

The objective of this study was to determine feasibility for a larger, future study that will define the effect of aerobic exercise on cellular, molecular, and functional measures in adults with mild-moderate asthma.
Design

Recruited subjects were randomized into usual care (sedentary) or usual care with moderate intensity aerobic exercise treatment groups.
Setting / Participants

Nineteen adults with mild-moderate asthma but without a recent history of exercise were recruited at the UAB Lung Health Center, Birmingham, AL.

Intervention

The exercise group underwent a 12?week walking program exercising at 60 – 75% of maximum heart rate (HRmax). Subjects self-monitored HRmax levels using heart rate monitors; exercise diaries and recreation center sign-in logs were also used.

Main outcome measures

Functional measures, including lung function and asthma control scores, were evaluated for all subjects at pre- and post-study time-points; fitness measures were also assessed for subjects in the exercise group. Peripheral blood and nasal lavage fluid were collected from all subjects at pre- and post-study visits in order to evaluate cellular and molecular measures, including cell differentials and eosinophilic cationic protein (ECP).
Results

Sixteen subjects completed the prescribed protocol. Results show that subjects randomized to the exercise group adhered well (80%) to the exercise prescription and exhibited a trend toward improved fitness levels upon study completion. Both groups exhibited improvements in ACQ scores. No changes were observed in lung function (FEV1, FEV1/FVC), cell differentials, or ECP between groups.
Conclusions

Results indicate that a moderate intensity aerobic exercise training program may improve asthma control and fitness levels without causing asthma deterioration in adult asthmatics. As such, these findings demonstrate the feasibility of the study protocol in preparation for a larger, clinical trial that will elucidate the functional consequences of aerobic exercise on asthmatic cellular and molecular responses.
Background

Asthma is characterized by the symptoms of wheezing, chest tightness, dyspnea and cough, and by the presence of reversible airway narrowing and/or airway hyperresponsiveness (AHR) to bronchoconstrictor stimuli. Although multifactorial in origin, asthma is considered an inflammatory process that is the result of an inappropriate immune response to common stimuli. Previous studies have demonstrated that increased levels of inflammatory mediators, such as serum eosinophilic cationic protein (ECP), correlate positively with asthma exacerbations and worsening [1,2].

Increasing evidence indicates that decreased physical activity may play a role in the severity and increasing prevalence of asthma [3]. We and others have reported that, in murine asthma models, repeated bouts of aerobic exercise at a moderate intensity attenuate both airway inflammation and hyperreactivity significantly [4-7]. Furthermore, several clinical studies suggest that aerobic exercise training, as a part of a pulmonary rehabilitation program, improves asthma control and overall physical fitness of asthmatics and reduces their disease-related hospital admissions [3,8-10]. In accordance with these studies, the American College of Sports Medicine (ACSM) and the American Thoracic Society (ATS) recommend the implementation of low to moderate intensity aerobic exercise for asthmatic patients [11,12]. Specifically, the ACSM suggests walking or other forms of exercise that utilize large muscle groups 3–5?days per week at 50% of maximal exertion. The ATS recommends exercising at 60 to 75% of maximal work rate for 20 to 30 minutes per day 2 to 5?days per week, and our study follows the ATS guidelines for exercise.

Despite these reports and recommendations, however, the physiologic basis for the clinical improvement that many asthmatics experience with a regular exercise program is not understood fully. The objective of this pilot study was to determine feasibility for a larger, future study that will define the effect of moderate intensity aerobic exercise on cellular, molecular, and functional measures in adults with mild-moderate severity asthma. Nineteen subjects were randomized into two treatment groups: usual care (sedentary) or usual care with moderate intensity aerobic exercise. Subjects in the exercise group underwent a 12?week walking program exercising at 60 – 75% of maximum heart rate (HRmax). Outcome indicators included functional (lung function, ACQ, fitness), cellular (circulating cell differentials), and molecular (pro-inflammatory mediators, including ECP) measures. Results show that subjects randomized to the exercise group adhered well (80%) to the exercise prescription and exhibited a trend toward improved fitness levels as compared with sedentary controls. Both groups exhibited improvements in Asthma Control Questionnaire (ACQ) scores. No changes were observed in lung function (FEV1, FEV1/FVC), cell differentials, or pro-inflammatory mediator levels, including ECP, between groups. Despite these observations, we maintain that this current study demonstrates the feasibility of the protocol in preparation for a larger clinical trial that will elucidate the functional consequences of aerobic exercise on cellular and molecular responses in asthmatic patients.
Methods
Subjects

This randomized, parallel group proof of concept study was approved and monitored by the UAB Institutional Review Board. Subjects were recruited from the University of Alabama at Birmingham (UAB) Lung Health Center’s Asthma Clinical Research Database from March 2009 through June 2011. Adults with mild-moderate persistent asthma (as defined by the NAEPP guidelines [13]) with at least a 12% FEV1 reversibility were eligible for enrollment. A physician diagnosis of asthma and documentation of reversible airflow obstruction was utilized to exclude patients with other causes of dyspnea. Individuals who underwent aerobic exercise regularly (3 or more times per week for more than 20 minutes at a time) during any of the six months prior to the study were not eligible for enrollment in order to facilitate the examination of exercise-mediated effects on asthmatic responses. In addition, individuals who smoked within 6?months from the start of the exercise protocol or with greater than a 10 pack year smoking history were excluded in order to exclude patients with chronic obstructive pulmonary disease (COPD). Individuals with other major illnesses, including coronary artery disease, congestive heart failure, stroke, severe hypertension, immunodeficiency states, or other conditions that would have interfered with participation in the study or with the proposed measurements were not eligible. In order to facilitate high adherence and data collection rates, individuals who were unable or unwilling to provide consent, perform the exercise protocol, provide pre- and post-study measurements, be contacted via telephone, or who intended to move out of the area within 6?months from the start of the study were excluded. Figure 1 illustrates the number of subjects screened and enrolled in the study.

thumbnailFigure 1. CONSORT figure of subject screening and recruitment. Fifty subjects were interviewed; thirty-one were excluded or refused. The remaining subjects were randomized into education and education with exercise treatment groups. A total of three subjects (1 – education; 2 – education/exercise) were withdrawn from the study because of protocol violations.
Interventions

Subjects were recruited by the study coordinator and randomly assigned to either usual care or usual care with moderate intensity aerobic exercise treatment groups (Figure 1). Permuted variable size block randomization developed by the biostatistician was used to allocate subjects to the two study arms. The variable block size prevented exact knowledge of the next randomization assignment while maintaining equal allocation of subjects to the study arms throughout the study. All subjects were provided with two zippered pillow encasements and one mattress protector (Royal Heritage). These items were membrane free materials with a pore size less than 5% to reduce subject exposure to dust mite and dander in their bedding. In addition, study subjects randomized to the moderate intensity aerobic exercise group received a 3?month free membership to a local exercise facility at the time of the initial visit. This allowed the study subject a secure and safe environment in which to perform the exercise protocol. This strategy was designed to reduce adverse events associated with allergen exposure as well as prevent drop outs due to difficulty obtaining a location within which to perform the exercise protocol.
Usual care asthma education

All subjects received a brief (approximately 30 minute) coordinator-led educational intervention at the UAB Lung Health Center. Educational content focused on: i) the role of inflammation in asthma, ii) allergens that can trigger airway inflammation, iii) tips for avoiding or reducing exposure to triggers categorized as allergens (dust, bedding, furniture, pollens, food allergies, animal dander, mold, cockroaches), iv) caring for pillow and mattress covers, and v) good health practice (getting eight hours of sleep a day, drinking plenty of fluids, relaxing, eating a balanced diet and reducing stress).
Moderate intensity aerobic exercise

Those randomized to the moderate intensity aerobic exercise group completed a 12-week exercise training program at a frequency of 3 times per week, 30 minutes each session, at a steady-state intensity that achieved 60 – 75% of maximum heart rate (HRmax). In order to determine each subject’s HRmax and fitness level, subjects performed a mandated graded treadmill test to volitional fatigue using a modified version of the Bruce protocol [14]; this test was performed at the UAB Clinical Exercise Facility. Subjects’ fitness levels were measured in the same manner at the conclusion of the 12-week intervention. Because subjects were using medications which may have influenced heart rate (such as bronchodilators), we utilized the graded treadmill test to allow us to measure subjects’ true maximum heart rates while taking their usual medications; Ratings of Perceived Exertion were recorded throughout the treadmill test. Maximal oxygen uptake in one minute (VO2max), as measured with a metabolic cart, was accepted as accurate if at least 2 of 3 physiologic criteria were met: leveling off of VO2 with increasing workload, respiratory exchange ratio (RER)?>?1.15, and heart rate equal to age-predicted maximum. The target heart rate range was then calculated for each subject.

Recommended exercise prescription included a 5 minute warm-up, 30 minutes of steady state exercise via walking, and a 5?min cool-down; thus total exercise time was 40 minutes per exercise bout. Compliance with this prescription was verified via heart rate monitor readings as described below. The exercise program was performed at the UAB Recreational Center and was completed in conjunction with standard patient education described above.
Subject visits

Subjects made three clinic visits to the UAB Lung Health Center. At the initial visit and prior to the start of the exercise protocol, all subjects underwent a complete physical with a board certified pulmonologist to ensure that the subjects were able to tolerate the exercise regimen. In addition, subjects completed health history and physical activity history questionnaires and documented asthma exacerbations at the initial visit. ECGs (12-lead) were used to permit safety monitoring of any previously un-diagnosed heart ailments and as part of the exercise testing for the subjects randomized to the exercise group. Lung function measurements and sample collection procedures (described below) were conducted at pre- and post-study intervals.
Exercise monitoring

Subjects randomized to the exercise treatment group were monitored for adherence to the exercise prescription. Throughout the study, aerobic exercise subjects were asked to wear a Polar Heart Rate Monitor (model 625X), which stores relevant exercise history information, including heart rate target zones, exercise duration in target zones, average heart rate, maximum heart rate, and total exercise time. Staff instructed subjects in the use of the heart rate monitor at the initial visit. Stored information, including length of the exercise session and average target heart rate during the exercise session, was downloaded onto a computer at the post-study visits. In addition, subjects kept a weekly exercise diary, which included the frequency of exercise, asthma-related symptoms and exacerbations, the use of pillow and mattress covers, and good health practices. Subjects submitted the exercise logs to the study coordinator at the post-study visits. Sign-in logs from the participating fitness center were monitored weekly in order to verify physical activity logs of subjects randomized to the exercise group. Subjects were called each week to ensure they were recording the exercise activity and to encourage adherence. In addition, phone calls permitted investigator evaluation of any increases in asthma symptoms, other health problems that interfered with their exercise prescription, or problems with heart rate monitors. It also provided direct feedback about non-compliance.

It is possible that subjects in the exercise group may have exhibited improved asthmatic responses as a consequence of increased interaction with or attention from individuals at the fitness center. In order to control for this interaction / attention within the exercise group, individuals in the usual care group also received weekly phone calls from the study coordinator. During these brief phone calls, the study coordinator asked the subject how he/she was doing and if there was anything related to his/her respective program with which he/she needed assistance.
Outcome indicators

The primary outcome indicator for this study was serum ECP. ECP is a marker of eosinophil activation found in both lavage fluids and serum of asthmatics. It has been demonstrated to correlate with asthma exacerbations and worsening as well as the effectiveness of asthma-related therapies [1,2]. Secondary outcome indicators included asthma control scores, airway and peripheral blood inflammatory markers (nasal lavage ECP, serum cytokines, peripheral blood immune cell populations), lung function parameters (FEV1, FEV1/FVC), and fitness measures (VO2 peak, HR peak, RER, total treadmill-time).
Sample collection

Subjects provided blood and nasal lavage samples at the pre- and post-study visits. The post-study visit was conducted approximately 24 hours after the last session of exercise and at the same time of day in order to minimize effects of circadian rhythms on sample content [4].
Blood draw

Peripheral blood (15?ml at each visit) was collected in apyrogenic, heparinized tubes (Vacutainer, Becton Dickinson). Serum was separated and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation on Ficoll-Paque (Pharmacia). Serum samples were quick frozen in a dry ice bath and stored at ?80°C until analysis; peripheral blood immune cells underwent immediate analyses.
Nasal lavage

Nasal lavage was performed with a disposable metered-dose pump filled with isotonic saline solution at room temperature [15]. Excessive mucus was first cleared by one spray of saline followed by a forceful exsufflation through the nostril. The same nostril was lavaged with 6?ml of the saline solution, which remained in the nasal cavity for approximately one minute and was then removed. Nasal lavage fluid (NLF) was then centrifuged to remove particulate matter and stored immediately at ?80°C.
Pro-inflammatory mediator analyses

Cytokine (ECP, IL-1?, IL-4, IL-5, IL-6, IL-13, TNF?) and total IgE content in serum and NLF were measured via enzyme linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (BioSource).
Cell differential analyses

Differential cell counts were performed on cells derived from peripheral blood as described previously [4]. Cell viability was determined via trypan blue exclusion and cell types were differentiated using Wright-Giemsa stain (Dade Behring Inc.). Cell differentials were determined from at least 500 leukocytes using standard hematological criteria.
Asthma control

Subjects completed the Juniper Asthma Control Questionnaire (ACQ) at initial and post-intervention study visits. Asthma control was determined by the score on the ACQ [16]. This instrument integrates common indicators of asthma control, including use of bronchodilators, nocturnal symptoms, cough, activity level, and pulmonary function. It assesses the full range of clinical impairment that patients with asthma experience and is highly sensitive to small changes in asthma control that are clinically significant. Scores range from 0 to 6. Lower scores reflect better control, and a difference of greater than 0.5 between the pre-study score and the post-study score is considered clinically significant. Scores greater than or equal to 1.5 indicate poorly-controlled asthma with a positive predictive value of 0.88 [16].
Pulmonary function analyses

Lung function was evaluated via spirometry using a portable Multispiro spirometer (Creative Biometrics) according to ATS/ERS guidelines [17]. Three forced vital capacity (FVC) maneuvers were performed for each subject and predicted values (FEV1, FVC) were determined.
Statistical analysis

Baseline characteristics between sedentary and moderate intensity groups were compared. Given the small sample size of the pilot study, paired comparisons were made using Fisher’s exact test for nominal characteristics (gender, smoking, race) and Wilcoxon Rank Sum for continuous measures (age, FEV1, etc.). Given the longitudinal nature of the study and the repeated outcome measures per subject, repeated measures analysis of variance techniques were applied to examine changes over time and to determine if the changes in outcomes over time differed by groups. Because repeated measures analysis of variance assumes normally distributed outcomes, distributional properties of the residuals from the repeated measures analysis of variance models were examined. Across all outcomes, only minor deviations from the normality assumption were observed.
Results
Protocol design and subjects

Nineteen subjects were recruited into this pilot study; 16 completed the protocol (Figure 1; see Table 1 for baseline subject characteristics). At the start of the study, ninety-four percent of subjects had poor asthma control (ACQ) as indicated by the Asthma Control Questionnaire (ACQ score???1.5) [18]. None of the baseline characteristics, including gender, age, race, asthma control, asthma duration, and smoking history, differed significantly between the two treatment groups (Table 1).

Table 1. Baseline subject characteristics
Adherence to prescribed aerobic exercise protocols

Because of faulty heart rate monitor recordings, exercise data from two subjects were incomplete; therefore, these subjects were dropped from all study analyses. Completed data from heart rate monitors and exercise logs indicated that subjects in the exercise group, on average, performed 32 out of 36 of the prescribed exercise bouts. Of the completed exercise bouts, 80% of these bouts were performed for the prescribed duration and in the prescribed target heart rate range.
Inflammatory mediators and circulating eosinophils

Figure 2 demonstrates that, at the post-study timepoint, subjects in both the sedentary and moderate intensity exercise groups exhibited no statistically significant differences in either circulating mediators, including serum ECP, or eosinophils. Subjects in the exercise group, however, exhibited a trend toward decreased eosinophilia, which was not observed in the sedentary subjects. No statistically significant differences were observed for the other circulating mediators, including IL-1?, TNF?, IL-4, IL-5, IL-6, and IL-13, as well as mediators in nasal lavage (data not shown).

thumbnailFigure 2. Changes in circulating ECP and eosinophils between sedentary and exercise treatment groups. Serum samples were collected from sedentary and exercise subjects at pre- and post-study timepoints. ECP levels in serum (A) were measured via ECP-specific ELISA. Cells were harvested from the peripheral blood at pre- and post-study timepoints. Differential cell counts for (B) eosinophils were performed as described in the text. Results are reported as percent of total peripheral blood immune cells. Black bars indicate average measurements in each group (education: n?=?8; exercise: n?=?6).
Asthma control

Figure 3 indicates that subjects in the exercise group experienced a mean improvement in asthma control of 0.22 over the study period compared to a mean change of 0.73 in the sedentary control group. Although these changes were not statistically significant between groups, such changes did exhibit a trend toward improved asthma control within each group. The sedentary group displayed a pronounced placebo effect with a change greater than 0.5, which is considered clinically significant [16,18]. It should be noted that one patient in the exercise group did experience an exacerbation during her 12?weeks of exercise, but this exacerbation did not appear to be triggered by the exercise program. Her study data were eventually discarded secondary to faulty heart rate monitor recordings, thus the overall study data were not confounded by this exacerbation.

thumbnailFigure 3. Changes in asthma control between sedentary and exercise treatment groups. Changes in asthma control were measured using the Asthma Control Questionnaire (ACQ). Black bars indicate average responses in each group (education: n?=?8; exercise: n?=?6).
Lung function parameters

Subjects in both treatment groups had post-bronchodilator spirometry performed at visits before and after completion of the study protocol; the FEV1 percent and the FEV1/FVC ratios of predicted for each subject were compared between these visits. Post-bronchodilator spirometry was chosen because home medications were not withheld prior to visits. As shown in Figure 4, there were no statistically significant changes in FEV1 percent and FEV1/FVC ratios for either treatment group.

thumbnailFigure 4. Changes in lung function between sedentary and exercise treatment groups. (A) FEV1 and (B) FEV1/FVC parameters were measured via spirometry in sedentary and exercise subjects at pre- and post-study timepoints. Results are reported as either percent predicted (FEV1) or percent actual (FEV1/FVC). Black bars indicate respective averages in each group (education: n?=?8; exercise: n?=?6).
Fitness levels

Parameters chosen to measure changes in fitness levels for subjects in the exercise group pre- and post-protocol completion included VO2 peak, HR peak, respiratory exchange ratio (RER), and total treadmill time during exercise testing [19]. At protocol completion, subjects in the exercise group exhibited significant increases in VO2 peak (mean change 2.64) and total treadmill time (mean change 1.39?min) (Figure 5A, D); changes in RER (mean change 0.04) and HR peak (mean change) displayed a similar trend (Figure 5B, C). RER should be greater than or equal to 1.1 with intense exercise. None of our subjects, however, reached an RER of 1.1 on maximal exercise, possibly due to ventilation impairment.

thumbnailFigure 5. Changes in fitness levels in exercise subjects. Subjects randomized to the exercise treatment group performed a mandated graded treadmill test to volitional fatigue using a modified version of the Bruce protocol both before and upon protocol completion. Fitness measures included A) VO2 peak, B) HR peak, C) respiratory exchange ratio (RER), and D) total treadmill-time. Black bars indicate average responses in each group (*p???0.04 as compared with pre-study measurements; education: n?=?8; exercise: n?=?6).
Discussion

The use of an exercise group and a sedentary group permitted direct comparison of the effectiveness of moderate intensity aerobic exercise plus education versus education only on asthma-related responses. Interventions which require a behavior change dictate the recruitment of motivated individuals; however, all subjects recruited to our study were informed that they could be randomized to the exercise group prior to signing consent. Although not all subjects were assigned to the exercise group, several potential biases (including differential attrition) which threaten the validity of a study design that includes a sedentary control group were addressed by recruiting only subjects who were willing to engage in a moderate intensity aerobic exercise protocol for twelve weeks.

Results suggest that exercise training at a moderate intensity improved asthma control and fitness measures in adult asthmatics; however, the final sample did not achieve sufficient statistical power to determine significant differences in most outcome measures. Because all subjects received education instruction in allergen avoidance, as well as pillow and mattress protectors, it is possible that the sedentary group may have included a greater proportion of atopic asthmatics; the atopic status of each of the subjects was not known. If this was indeed the case, the presence of atopy could have biased against the effect of exercise, since avoidance would have possibly improved asthma control and, thereby, diminished the observed effectiveness of the exercise intervention.

Although the majority of subjects self-reported having poorly controlled asthma, neither the mean circulating ECP levels nor eosinophil counts were elevated in these subjects. Despite this observation, subjects in the exercise group exhibited a trend toward decreased circulating eosinophils; however, the serum ECP levels in these subjects were unchanged. Such discordance between ECP levels and eosinophil counts may be due to exercise-mediated release of ECP from activated eosinophils as they traffic out of the circulation and into the vasculature, including the airway mucosa. Previous studies, which have reported elevation of serum ECP levels with a concomitant decrease in eosinophils following exercise, support this hypothesis. In these earlier studies, serum ECP levels and circulating eosinophils were measured during sessions of acute graded aerobic exercise [20] and endurance aerobic exercise at moderate altitude [21] in healthy subjects. In both studies, serum samples were collected within minutes post exercise. Both reports demonstrated that serum ECP levels were elevated while eosinophils counts decreased following the single, respective exercise session. In contrast, additional studies have demonstrated that physical activity has differential effects on the circulating levels of other cytokines, including IL-6 and TNF? [22-24]. These previous studies differ with the present study in exercise duration, frequency, subject fitness level, and/or timing of sample collection. As such, the differences in the observed effects of aerobic exercise on ECP and serum cytokine measurements between the present and previous studies are likely due to such exercise-related variables [25-30]; further, these differences underscore the need for additional study.

Completion and analyses of the current pilot study highlighted several areas that will need to be redefined in preparation for a future, larger study. ECP, which has been reported to correlate positively with asthma exacerbations and worsening [1,2], was chosen initially as a primary outcome measure because the objective of the future study is to test the functional consequences of aerobic exercise on asthmatic cellular and molecular responses. As observed in this current study, the choice of serum ECP as the primary outcome may have lacked sensitivity for assessing the effects of exercise on eosinophilic inflammation; therefore, sputum ECP levels and eosinophil counts, which better reflect the airway inflammation, will be used in the future study. In addition, revised inclusion criteria will require that subjects demonstrate eosinophilic inflammation at baseline in order ensure that any impact of exercise on this outcome can be observed. Baseline data will also include information on measures of subjects’ atopy in order to ensure that subjects with atopic responses are evenly distributed between the sedentary and exercise groups. Clinical outcome measures will be expanded to include additional lung function parameters, such as ventilatory capacity and exercise-induced bronchospasm (EIB). Previous results reported by Emtner and colleagues demonstrated that adults with mild-moderate asthma who underwent a high intensity exercise (80-90% predicted HRmax) swimming program for 10?weeks exhibited increased ventilatory capacity, decreased EIB, and decreased asthma-related symptoms [31].
Conclusions

Results from this pilot study suggest that aerobic exercise training at a moderate intensity may improve asthma control and fitness levels in the absence of asthma exacerbations in adult asthmatics. Strong adherence to the exercise protocol demonstrates the feasibility of the protocol in preparation for a larger, clinical trial that will test the effects of exercise on the cellular, molecular, and functional outcome measures of the asthmatic response. Such increased understanding will lead to the elucidation of the potential mechanisms that underlie the beneficial effects of moderate intensity exercise on asthmatic responses. Moreover, this understanding may lead to the development of novel therapeutic approaches, including the use of moderate intensity aerobic exercise as an adjunct therapy, for the treatment of this chronic disease.

Courtesy of http://www.aacijournal.com/content/8/1/13

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Severe Asthma and COPD Readmissions and Exacerbations

If you or someone you know suffers from severe Asthma and or COPD then you owe it to yourself and to others to listen in on this interview with Chris Garvey FNP, MSN, MPA, FAACVPR Manager, Seton Pulmonary & Cardiac Rehabilitation that took place at the California Thoracic Society (CTS) 2013 Conference Carmel California.

Key take aways:

•The importance of exercise
•Taking your meds
•The benefits of multidisciplinary teams
•Early identification
•Effective treatment based on evidence based guidelines to reduce Exacerbation’s
•Reduced cost of care
•Effective Care
•Understand your symptoms
•Education
•Honest and frank discussion your doctor and or health care provider
•Getting the right meds
•Follow up with your doctor and or health care provider

For additional information about Asthma and COPD Overlap Syndrome check out http://asthmacopdoverlapsyndrome.org

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BPA Raises Risk for Childhood Asthma Study Finds

Children exposed to the plastics chemical bisphenol A had an elevated risk for asthma

Researchers at the Columbia Center for Children’s Environmental Health at the Mailman School of Public Health are the first to report an association between early childhood exposure to the chemical bisphenol A (BPA) and an elevated risk for asthma in young children. BPA is a component of some plastics and is found in food can liners and store receipts.

In this three minute interview with Robin M. Whyatt, DrPH Professor of Environmental Health Sciences at the Columbia University’s Mailman School of Public Health we learn about the chemical bisphenol A (BPA) and the Risk for Asthma.

Specifically we learn about:

•Key findings of the study including the levels of BPA in our system
•The link between BPA and Asthma and lung inflammation
•The need for additional research
•Tips to reduce exposure to BPA
•Benefits of fruits and vegetables and the reduction of BPA
•The levels of BPA and plastic and how to measure
•Tips to prepare and store food that will reduce BPA exposure

Results appear in the March edition of the Journal of Allergy and Clinical Immunology.

“Asthma prevalence has increased dramatically over the past 30 years, which suggests that some as-yet-undiscovered environmental exposures may be implicated. Our study indicates that one such exposure may be BPA,” says lead author Kathleen Donohue, MD, an assistant professor of Medicine at Columbia University College of Physicians and Surgeons and an investigator at the Center for Children’s Environmental Health.

Dr. Donohue and her co-investigators followed 568 women enrolled in the Mothers & Newborns study of environmental exposures. BPA exposure was determined by measuring levels of a BPA metabolite in urine samples taken during the third trimester of pregnancy and in the children at ages 3, 5, and 7. Physicians diagnosed asthma at ages 5 to 12 based on asthma symptoms, a pulmonary function test, and medical history. A validated questionnaire was used to evaluate wheeze.

After adjusting for secondhand smoke and other factors known to be associated with asthma, the researchers found that post-natal exposure to BPA was associated with increased risk of wheeze and asthma. BPA exposure during the third trimester of pregnancy was inversely associated with risk of wheeze at age 5. This unexpected finding is in contrast to the results of a previous study, which found that BPA exposure during the second trimester, a critical period for the development of airways and the immune system, was positively linked with risk for asthma.

Increased risk for wheeze and asthma was seen at “fairly routine, low doses of exposure to BPA,” says Dr. Donohue. “Like most other scientists studying BPA, we do not see a straightforward linear dose-response relationship.”

At all three time points, more than 90% of the children in the study had detectable levels of BPA metabolite in their bodies, a finding that is in line with previous research. This does not mean that they will all develop asthma, cautions Dr. Donohue. “Just as smoking increases the risk of lung cancer but not everyone who smokes gets lung cancer, not every child exposed to BPA will develop asthma.”

The biological mechanism behind the BPA-asthma connection is unclear. The current study found no evidence that exposure to BPA increased the risk that the immune system would develop more antibodies to common airborne allergens. “Other possible pathways may include changes to the innate immune system, but this remains an open question,” says Dr. Donohue.

The new study builds on existing evidence linking BPA exposure to respiratory symptoms, as well as to obesity, impaired glucose tolerance, and behavioral issues, among a range of health problems. In July, the Food and Drug Administration banned BPA in baby bottles and sippy cups.

“It is very important to have solid epidemiologic research like ours to give the regulators the best possible information on which to base their decisions about the safety of BPA,” says senior author Robin Whyatt, DrPH, professor of Environmental Health Sciences and deputy director of the Columbia Center for Children’s Environmental Health.

To reduce exposure to BPA, the National Institute of Environmental Health Sciences (NIEHS) recommends avoiding plastic containers numbers 3 and 7, eating less canned food, and, when possible, choosing glass, porcelain, or stainless steel containers, especially for hot food and liquids.

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High Risk Factors in Asthma-COPD Overlap Syndrome

High Risk Factors in Asthma-COPD Overlap Syndrome: Highly Prevalent But Grossly Underappreciated

By Tinka Davi, World Asthma Foundation

The statistics are staggering:
Every four minutes someone dies of COPD or chronic obstructive pulmonary disease.
Every day nine people die from asthma.
But what takes a higher toll is a combination of the two diseases, which is recognized as Asthma-COPD Overlap Syndrome or ACOS.

Because this syndrome has not received much attention by the medical community, the frequency of deaths due to ACOS alone has not been compiled.

ACOS, which was formerly called “asthmatic bronchitis,” is a commonly experienced, yet loosely defined clinical entity. It accounts for approximately 15 to 25 percent of the general population of obstructive airway diseases who experience worse outcomes compared to asthma or COPD alone.

Patients with ACOS have the combined risk factors of smoking and atopy such as hay fever. These adults are generally younger than patients with COPD and experience acute exacerbations or attacks of their breathing requiring immediate attention with higher frequency and greater severity than lone COPD.

Physicians and other healthcare professionals at UC Davis have taken their clinical experience and research nationally to increase public awareness.

“ACOS is concerning because it’s much worse in terms of exacerbations, or acute attacks of breathlessness, as compared to COPD.” said Amir Zeki, MD, assistant professor of medicine pulmonary, critical, and sleep medicine at the Center for Comparative Respiratory Biology and Medicine at the University of California Davis School Of Medicine.

Samuel Louie, MD and Amir Zeki, MD

Samuel Louie, MD and Amir Zeki, MD

Exacerbation is an acute flare up or worsening of the disease usually over two to three days that causes patients with asthma, COPD or both to seek immediate medical attention and a change in their daily medications.

An exacerbation is a flare up or worsening of the disease, otherwise known as an “attack.”

With an acute attack, the risk of hospitalization, need for steroids, days of missed work or school increases with ACOS, Zeki said. The prevalence of frequent exacerbations in ACOS is nearly two-and-a-half times higher than COPD and risk of severe exacerbations in ACOS is twice as high as COPD.

Zeki and Samuel Louie, MD are collaborating efforts to educate the medical field and the public about ACOS.

Louie, professor of medicine, is director of the UC Davis Asthma Network (UCAN) since 1998 and director of the UC Davis Reversible Obstructive Airway Disease (ROAD) Center, which serves adults and adolescents in Northern California who have difficult to control asthma, bronchiectasis and COPD.

“We are entering a new era of public awareness of people living with chronic lung disease such as asthma and COPD,” Louie said. “Our mission at UC Davis is to transform health care by integrating and provide quality patient care services these conditions, which promote patient education and safety, social networking, and to align our goals with national efforts to transform people’s lives. But we can achieve success without recognizing the clear and present danger from not recognizing the Asthma-COPD Overlap syndrome.”

The incidence of ACOS is becoming more prevalent. “One in five patients in our clinic will likely have ACOS,” Zeki said.

Louie agrees. “When patients learn what they have, they begin to look for more information and help. That is where we have to be ready to provide comprehensive services that are integrated and coordinated to help patients and their families navigate the complex modern health care system,” he said.

That’s why the two physicians are zealous in their efforts in providing ACOS education, not only for patients but to the medical community which is not as familiar with the syndrome as it is with asthma or COPD. They’d also like to see extensive research for treatment options.

“There’s no cure for asthma and there’s no cure for COPD, but we can treat them to improve their quality of life and prevent acute exacerbations,” Zeki said.

However, standard treatment options are not as aggressive as needed to treat the asthma-COPD syndrome.

“It really all begins with empathy.” Louie said. “Empathy within healthcare providers for how asthma, COPD and ACOS patients suffer when they are given prescription drugs without education on an individual level. We have to ignite that empathy by increasing awareness and providing education.”

The two physicians are board members of the World Asthma Foundation, which provides educational resources that inform patients, medical professionals and the general public about the latest clinical advances, management and treatment options for asthma disorders, including ACOS.

“I am convinced that every patient who lives with asthma, COPD or ACOS has character and intelligence but what they often lack is willpower.” Louie said. “And when physicians and their colleagues think COPD is ‘irreversible,’ that is like a nail in the coffin to patients, but nothing could be further from the truth. There are no cures as Dr. Zeki said, but then there is no cure for diabetes or heart disease either.

“People with asthma, COPD and ACOS deserve better. It requires that we all take responsibility, patients too, but physicians must take their empathy one step further and realize how reversible asthma, COPD and ACOS can be” Louie said.

Willaim Cullifer, executive director of the World Asthma Foundation, said, “This is a fascinating new development in the understanding of asthma and COPD and it’s fantastic to be on the forefront of educating the public and the healthcare community about this issue.”

With their concern and enthusiasm for serving ACOS patients as well as those living with asthma alone or COPD alone, the dedicated physicians are bound to make a difference, hopefully in their lifetimes.
“My hope is to gain a better understanding of this syndrome, which may indeed be on the continuum of airway diseases such as COPD and asthma,” Zeki said. “We hope to garner the support and funding needed to study it given its high prevalence and public health significance.”

“When you get done taking care of the disease, you’re taking care of people,” Louie said.
“We must fight indifference. The only way to do that is to get the word out that we all have much more to achieve together to empower patients with reversible obstructive airway diseases.” Louie said.

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Asthma and Vaccine Research

Asthma Vaccine 4 to 5 years away says Researchers

The vaccine developed in a model of healthy mice was then optimized in a mouse model of asthma. In this model the vaccine triggers production of specific antibodies and cellular responses specific to Derf1, thus guiding the immune system response to a non-allergenic, protective when the allergen is encountered. The two injections required and administered 3 weeks apart have significantly reduced the airway hyperresponsiveness and levels of inflammatory cytokines that were however present in the lungs of asthmatic mice unvaccinated.

Researchers have therefore designed a technique of DNA-based immunization of the allergenic substance. “Rather than administering allergen extracts repeatedly to reduce the sensitivity, we worked from specific DNA sequences (the allergen) responsible for the allergy. Some studies have shown the therapeutic potential of this strategy but we had to find techniques ensuring feasibility in humans, explains Bruno Pitard, Team Director for Innovative Biotherapy at Institute of the thorax (CNRS / INSERM / University of Nantes). The translation to humans does require treatment to be effective from a low dose of DNA injected.

The researchers first sought to prove the efficacy of this DNA-based immunization against the specific allergen, Derf1 in a relevant animal model developed by the team Bronchial Diseases Allergies and directed by Antoine Magnan. In Europe, Dermatophagoides farinae 1 (Derf1) is indeed a very common allergen carried by the mite Dermatophagoides farinae. More than half of patients allergic to dust mites produce specific IgE antibodies (Derf1) against this substance and disease characteristics

In practice, researchers have used the genetic sequences of interest encoding theallergen Derf1 associated with a nanovector consisting of a synthetic polymer. This DNA sequence, carried by a sort of “molecular taxi” in muscle cells, providing the protein synthesis of the allergen, has modulating the allergic response to dust mites in asthmatic animals (1).

These new results validate the potential of this new nanovector for DNA vaccination, and is under regulatory preclinical development for future clinical trials in humans.

These new results validate the potential of this new nanovector for DNA vaccination, and is under regulatory preclinical development for future clinical trials in humans.

describe an innovative vaccine against one of the most encountered allergens in asthmatic patients . Direct administration of the vaccine into the muscle of a mouse model of asthma significantly reduces the sensitivity to the allergen and the associated inflammatory response.

Researchers have therefore designed a technique of DNA-based immunization of the allergenic substance. “Rather than administering allergen extracts repeatedly to reduce the sensitivity, we worked from specific DNA sequences (the allergen) responsible for the allergy. Some studies have shown the therapeutic potential of this strategy but we had to find techniques ensuring feasibility in humans, explains Bruno Pitard, Team Director for Innovative Biotherapy at Institute of the thorax (CNRS / INSERM / University of Nantes). The translation to humans does require treatment to be effective from a low dose of DNA injected

An Effective Asthma Vaccine by Intramuscular Injection Shows Promise Says Researchers

Asthma is a chronic inflammatory disease caused by breathing and an abnormal reactivity against allergens from the environment. Among the new directions currently in development, immunization is a promising approach says researchers. In a publication to appear in the journal Human Gene Therapy, researchers from Inserm and CNRS (“Institute of the thorax” CNRS / INSERM / University of Nantes) describe an innovative vaccine against one of the most encountered allergens in asthmatic patients . Direct administration of the vaccine into the muscle of a mouse model of asthma significantly reduces the sensitivity to the allergen and the associated inflammatory response.

Allergic asthma is a chronic respiratory disease affecting 300 million people worldwide. The number of individuals with asthma has doubled over the past decade and nearly 250,000 people die prematurely each year because of this affection. In most cases, asthma is caused by an abnormal reactivity to environmental substances known as allergens. From a physiological point of view, this hypersensitivity results in significant inflammation in the bronchi and bronchioles of individuals. Their ability to breathe properly is
then altered.

Current treatment involves the administration of corticosteroids to treat the symptoms and temporarily suspend the disease without curing it. An alternative treatment and perennial allergic asthma is based on a protocol-specific immunotherapy commonly called “desensitization.” Repeated administration of increasing doses of allergen is to reduce hypersensitivity and reduce symptoms during subsequent exposure. However, the effectiveness of this protocol is limited and highly variable among patients.

Researchers have therefore designed a technique of DNA-based immunization of the allergenic substance. “Rather than administering allergen extracts repeatedly to reduce the sensitivity, we worked from specific DNA sequences (the allergen) responsible for the allergy. Some studies have shown the therapeutic potential of this strategy but we had to find techniques ensuring feasibility in humans, explains Bruno Pitard, Team Director for Innovative Biotherapy at Institute of the thorax (CNRS / INSERM / University of Nantes). The translation to humans does require treatment to be effective from a low dose of DNA injected.

The researchers first sought to prove the efficacy of this DNA-based immunization against the specific allergen, Derf1 in a relevant animal model developed by the team Bronchial Diseases Allergies and directed by Antoine Magnan. In Europe, Dermatophagoides farinae 1 (Derf1) is indeed a very common allergen carried by the mite Dermatophagoides farinae. More than half of patients allergic to dust mites produce specific IgE antibodies (Derf1) against this substance and disease characteristics

In practice, researchers have used the genetic sequences of interest encoding theallergen Derf1 associated with a nanovector consisting of a synthetic polymer. This DNA sequence, carried by a sort of “molecular taxi” in muscle cells, providing the protein synthesis of the allergen, has modulating the allergic response to dust mites in asthmatic animals (1).

The vaccine developed in a model of healthy mice was then optimized in a mouse model of asthma. In this model the vaccinetriggers production of specific antibodies and cellular responses specific to Derf1, thus guiding the immune system response to a non-allergenic, protective when the allergen is encountered. The two injections required and administered 3 weeks apart have significantly reduced the airway hyperresponsiveness and levels of inflammatory cytokines that were however present in the lungs of asthmatic mice unvaccinated.

These new results validate the potential of this new nanovector for DNA vaccination, and is under regulatory preclinical development for future clinical trials in humans.

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Asthma Med Co-Payments Could Affect What Kids get their Asthma Medication Says Study

According to published reports by the Journal of the American Medical Association, health plans have implemented policies to restrain prescription medication spending by shifting costs toward patients. It is unknown how these policies have affected children with chronic illness.

The studies objective to analyze the association of medication cost sharing with medication and hospital services utilization among children with asthma, the most prevalent chronic disease of childhood.

The conclusion was greater cost sharing for asthma medications was associated with a slight reduction in medication use and higher rates of asthma hospitalization among children aged 5 years or older.

Design, Setting, and Patients Retrospective study of insurance claims for 8834 US children with asthma who initiated asthma control therapy between 1997 and 2007. Using variation in out-of-pocket costs for a fixed “basket” of asthma medications across 37 employers, we estimated multivariate models of asthma medication use, asthma-related hospitalization, and emergency department (ED) visits with respect to out-of-pocket costs and child and family characteristics.

Main Outcome Measures Asthma medication use, asthma-related hospitalizations, and ED visits during 1-year follow-up.

Results
The mean annual out-of-pocket asthma medication cost was $154 (95% CI, $152-$156) among children aged 5 to 18 years and $151 (95% CI, $148-$153) among those younger than 5 years. Among 5913 children aged 5 to 18 years, filled asthma prescriptions covered a mean of 40.9% of days (95% CI, 40.2%-41.5%). During 1-year follow-up, 121 children (2.1%) had an asthma-related hospitalization and 220 (3.7%) had an ED visit. Among 2921 children younger than 5 years, mean medication use was 46.2% of days (95% CI, 45.2%-47.1%); 136 children (4.7%) had an asthma-related hospitalization and 231 (7.9%) had an ED visit. An increase in out-of-pocket medication costs from the 25th to the 75th percentile was associated with a reduction in adjusted medication use among children aged 5 to 18 years (41.7% [95% CI, 40.7%-42.7%] vs 40.3% [95% CI, 39.4%-41.3%] of days; P = .02) but no change among younger children. Adjusted rates of asthma-related hospitalization were higher for children aged 5 to 18 years in the top quartile of out-of-pocket costs (2.4 [95% CI, 1.9-2.8] hospitalizations per 100 children vs 1.7 [95% CI, 1.3-2.1] per 100 in bottom quartile; P = .004) but not for younger children. Annual adjusted rates of ED use did not vary across out-of-pocket quartiles for either age group.

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Asthma and Mobile Monitoring Fails Value Muster

Findings published in the British Medical Journal show that patients who used mobile phones to monitor their asthma, did not improve control of the disease when compared to paper monitoring.

It also found that the use of mobile phone monitoring was considerably more expensive, leading researchers to conclude that it was not as cost effective overall.

The researchers who were funded by Asthma UK, randomized 288 patients with poorly controlled asthma to use either the t+ Asthma app on their smartphone, or the traditional paper monitoring method.

The app enabled twice-daily recording and transmission of symptoms, drug use, and peak flow. Patients in the control group were asked to keep a paper diary, recording the same data as the mobile group, again twice daily.

They wanted to see whether using the app would increase self-management of the patient’s asthma, but the results showed that there was no significant difference in the change in asthma control or self-efficacy between the two groups.

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Asthma and Bacteria: Exposure May Help Body Beef Up Immunity, Study Says

Asthma and Bacteria: Exposure May Help Body Beef Up Immunity, Study Says

The research was done in mice, but it supports the “hygiene hypothesis”: the idea that bacteria are needed to shape a healthy immune system, and that our bacteria-fearing lifestyles are increasing levels of asthma, allergy and other autoimmune diseases.

In the study, which was published in the journal Science, the researchers compared normal mice with mice that were raised in special germ-free environments. They found high levels of special white blood cells called invariant natural killer T cells (iNKT) in the lungs and intestines of the germ-free mice.

These iNKT cells release proteins that cause inflammation and attract more inflammatory white blood cells. Inflammation plays an important role in many autoimmune diseases, and iNKT cells are known to be an active ingredient in asthma, which is in the lungs, and ulcerative colitis, an inflammatory disease of the bowel.

Even when exposed to normal bacteria later in life, the germ-free mice still had abnormally high levels of iNKT cells and diseased lungs and intestines. This indicated that an “immune priming event” happens very early in life and is essential for the proper formation of the immune system, the researchers said.

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Asthma and Second Hand Smoke

Press reports reflect that new studies suggests kids who live with a smoker are more likely to wheeze or get asthma, providing more evidence for the link between secondhand smoke and breathing problems.

Researchers found that the biggest effect on wheeze and asthma symptoms was seen in babies and toddlers whose moms smoked while they were pregnant or soon after kids were born.

The findings don’t prove that secondhand smoke caused kids to get asthma, but they add to other research suggesting smoke exposure may trigger respiratory problems in youngsters, researchers said.

“What this really clearly demonstrates is that the research and data documenting the adverse effects of tobacco smoke exposure on children’s asthma is very strong,” said Dr. Harold J. Farber, who studies smoking exposure and asthma at Baylor College of Medicine and Texas Children’s Hospital in Houston.

He said kids’ lungs may be weaker when they’re exposed to smoke in the womb, and asthma drugs may not work as well in those children.

“Eliminating our children’s tobacco exposure has got to be a critical public health priority,” Farber, who wasn’t involved in the report, told Reuters Health.

Researchers from the UK analyzed more than 70 studies published between 1997 and 2011, all of which asked about smoking by parents or other household members and then tracked which kids were diagnosed with wheezing or asthma going forward.

Those studies showed that when moms smoked while they were pregnant, their kids were 28 to 52 percent more likely to wheeze, depending on the age they were assessed. The effect on asthma symptoms was greatest in babies and toddlers, who were 85 percent more likely to have asthma if they were exposed to smoke in the womb.

When moms or non-parent household members smoked, kids had up to a 70 percent higher chance of wheezing through age four, but the link to full-on asthma was less clear. The effect of maternal smoking was weakest in kids age five to 18.

There was limited data on how smoking by dads affected kids’ chances of wheezing or getting asthma, according to findings published Monday in Pediatrics.

Tricia McKeever from the University of Nottingham and her colleagues said their findings suggest that secondhand smoke has more of an influence on wheeze and asthma than researchers had previously estimated.

“Before, (secondhand smoke) was known as triggering an attack or exacerbating asthma,” said Geoffrey Fong, a tobacco researcher from the University of Waterloo in Canada.

“This study shows that secondhand smoke may cause the development of asthma,” and not just trigger attacks in kids who already have it, said Fong, who wasn’t involved in the new study.

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Asthma Study Goes High Tech

The Courier-Journal is reporting that Louisville, KY is going high-tech to try to figure out what’s behind the city’s problem with asthma. ‘Smart’ emergency inhalers will help those in Louisville metro area track causes with a data-driven asthma study.

As many as 500 Louisville residents will be equipped with “smart” emergency inhalers that will track the time and location of their asthma attacks.

It’s part of a study scheduled to begin in May that could help city officials understand what’s causing asthma attacks and help patients better manage the illness, which affects more than 100,000 people in the Louisville metro area.

The Louisville mayor’s office will announce the study this morning. It will coincide with a scheduled announcement by IBM that the company has selected Louisville to receive about $400,000 in technical support for the research as part of the company’s “Smarter Cities Challenge.”

IBM’s experts will help Louisville identify and analyze large volumes of data — from air quality to pollen outbreaks to traffic congestion — that can be compared with the information from the participants’ inhalers.

The result should shed new light on the city’s growing asthma problem, said Ted Smith, Louisville’s economic growth and innovation director.

The study uses technology developed by a Wisconsin company called Asthmapolis.

A small sensor is placed atop emergency inhalers that asthma patients use when they are having severe attacks, said David Van Sickle, the company’s co-founder who formerly worked in public health surveillance for the CDC.

When people use the inhaler, the sensor works with the patient’s cellphone to transmit the time of the attack to the company’s computer network. The patient’s cellphone, if it’s equipped with global-positioning software, also will send the location, Van Sickle said.

Working with the CDC, the company has experimented with the technology in two pilot projects of about 40 patients each, he said. One was in Wisconsin and the other in rural areas across several Midwestern states, he said.

Louisville is one of 33 cities chosen worldwide this year by IBM as part of its three-year, 100-city $50 million philanthropic initiative aimed at improving urban life, said Michael Rowinski, an IBM spokesman.

No money comes from IBM, just expertise, but that is more than enough for Louisville Mayor Greg Fischer.

“This project is unique because it brings together innovation, public health and data to help better understand our problem with asthma in Louisville,” Fischer said. “The brain power that IBM will bring to our city is even more valuable than dollars.”