E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies.

BACKGROUND: Use of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults, but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorders from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies. METHOD: We conducted a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with COPD. We discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection and genetic expression. RESULTS: Epidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (aOR) was 1.39 (95% CI 1.28-1.51); for COPD (n=9 studies) the aOR was 1.49 (95% CI 1.36-1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls, although sometimes less than for cigarettes. CONCLUSIONS: The evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose-response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of concern for respirology and public health.

E-cigarette use and asthma in a multiethnic sample of adolescents.

There is minimal evidence from epidemiological studies on how e-cigarette use is related to health indices in adolescence. We hypothesized that e-cigarette use would be associated with asthma, controlling for demographics and cigarette smoking. The hypothesis was tested with cross-sectional data from a statewide sample of school students. Surveys were administered in classrooms in 2015 to adolescents in 33 high schools throughout the State of Hawaii. The sample (N=6089) was 50% female and mean age was 15.8years. Data were obtained on demographics; ever use and current (past 30days) use of e-cigarettes, combustible cigarettes, and marijuana; ever being diagnosed with asthma; and currently having asthma. Multinomial regression examined the association between e-cigarette use and asthma controlling for cigarette smoking, marijuana use, and six demographic covariates. Current e-cigarette use was associated with currently having (vs. never having) asthma (adjusted odds ratio [aOR]=1.48, CI 1.26-1.74) and with previously having (vs. never having) asthma (aOR=1.22, CI 1.07-1.40). This was independent of cigarette smoking, marijuana use, and other covariates. Smoking and marijuana were nonsignificant in the multivariate analysis. Blacks, Native Hawaiians, other Pacific Islanders, and Filipinos had higher rates of asthma compared with Asian Americans and Caucasians. We conclude that e-cigarette use by adolescents is independently associated with asthma. This finding is consistent with recent laboratory research on pulmonary effects from e-cigarette vapor. Implications for public health should be considered.

Priming the immune system for heart disease: a perspective on group A streptococci.

Although immune responses against group A streptococci and the heart have been correlated with antibodies and T cell responses against cardiac myosin, there is no unifying hypothesis about carditis caused globally by many different serotypes. Our study identified disease-specific epitopes of human cardiac myosin in the development of rheumatic carditis in humans. We found that immune responses to cardiac myosin were similar in rheumatic carditis among a small sample of worldwide populations, in which immunoglobulin G targeted human cardiac myosin epitopes in the S2 subfragment hinge region within S2 peptides containing amino acid residues 842-992 and 1164-1272. An analysis of rheumatic carditis in a Pacific Islander family confirmed the presence of potential rheumatogenic epitopes in the S2 region of human cardiac myosin. Our report suggests that cardiac myosin epitopes in rheumatic carditis target the S2 region of cardiac myosin and are similar among populations with rheumatic carditis worldwide, regardless of the infecting group A streptococcal M serotype.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

Disparate rates of persistent smoking and drug use during pregnancy of women of Hawaiian ancestry.

BACKGROUND: Significant disparity in smoking rates has been previously reported in pregnant and non-pregnant women of Native Hawaiian ancestry. Disparities in drug use rates have also been reported in non-pregnant women of Native Hawaiian ancestry. OBJECTIVE: We undertook this study to compare rates of smoking and drug use during pregnancy among women in Hawaii to see if these differences are associated with disparities in pregnancy complications among Native Hawaiian women. METHODS: Women were enrolled in the Pacific Research Center on Early Human Development study from July 2007 to January 2008, according to approved protocols. Persistent smoking was defined as self-reported smoking within 1 week of admission for labor. Drug use data was assessed by self-report, or if available, toxicology tests at the time of labor. RESULTS: There were 868 women enrolled in the study during this period. Women of Hawaiian/part-Hawaiian ancestry comprised 22% of the study population. Rates of persistent smoking and drug use among Hawaiian women were significantly higher than the remainder of the study population (21% and 8.3% vs. 7.8% and 2.1%, respectively, P < .001 for both). Methamphetamine use was associated with an almost 5-fold increase in preterm birth and smoking a 3.4% decrease in birth weights. DISCUSSION AND CONCLUSION: Women of Hawaiian ancestry continue to smoke and use illicit drugs during pregnancy at significantly higher rates than women of other ethnic groups in Hawaii. In addition to the immediate effects on pregnancy, long-term adverse outcomes of in utero exposures of the offspring remain an important health disparity.

E-cigarette use and respiratory disorder in an adult sample.

OBJECTIVES: Little evidence is available on the association of e-cigarettes with health indices. We investigated the association of e-cigarette use with diagnosed respiratory disorder among adults in data from the Behavioral Risk Factor Surveillance Survey (BRFSS). METHODS: The 2016 Hawaii BRFSS, a cross-sectional random-dial telephone survey, had 8087 participants; mean age was 55 years. Items asked about e-cigarette use, cigarette smoking, and being diagnosed by a health professional with (a) asthma or (b) chronic obstructive pulmonary disease. Multivariable analyses tested associations of e-cigarette use with the respiratory variables controlling for smoking and for demographic, physical, and psychosocial variables. RESULTS: Controlling for the covariates and smoking there was a significant association of e-cigarette use with chronic pulmonary disorder in the total sample (AOR = 2.58, CI 1.36-4.89, p < 0.01) and a significant association with asthma among nonsmokers (AOR = 1.33, CI 1.00-1.77, p < 0.05). The associations were stronger among nonsmokers than among smokers. Results were similar for analyses based on relative risk and absolute risk. There was also a greater likelihood of respiratory disorder for smokers, females, and persons with overweight, financial stress, and secondhand smoke exposure. CONCLUSIONS: This is the first study to show a significant independent association of e-cigarette use with chronic respiratory disorder. Several aspects of the data are inconsistent with the possibility that e-cigarettes were being used for smoking cessation by persons with existing respiratory disorder. Theoretical mechanisms that might link e-cigarettes use and respiratory symptoms are discussed.

A new approach for analyzing cellular infiltration during allergic airway inflammation.

A mouse model for allergic airway inflammation involving ovalbumin (OVA) sensitization and challenge has been developed that reproduces hallmark features of human asthma and has provided valuable insight into the mechanisms by which this disease occurs. Cellular infiltrate in lungs of mice used in this model have conventionally been evaluated using histological examination of tissue sections and light microscopic analysis of lung lavage samples. As an alternative or complementary approach for characterizing cellular infiltrate, we developed a multicolor fluorescence-activated cell sorter (FACS) method involving the simultaneous detection of seven different markers on lung cell suspensions: CD4, CD8, B220, CD11b, Gr-1, CD49b, and FcepsilonRI. Only some of these cell types increased in OVA-challenged mice compared to PBS controls, including the CD4(+), B220(+), CD11b(+), and FcepsilonRI(+) groups. We also examined subpopulations of cells for coexpression of these markers and dissected heterogeneous populations as further evaluation procedures to characterize the cellular infiltrate resulting from OVA challenge. Finally, we combined FACS with real-time PCR to analyze certain cell types in terms of mRNA levels for factors involved in asthma, including GATA-3 and IL-1beta. Overall, these FACS-based techniques provide a powerful approach for analyzing cellular profiles in lung tissue from mice used in the mouse model of asthma and may also prove valuable in evaluating cellular infiltrates for other models of inflammation and immune responses.

Disparate Rates of Utilization and Progression to Combined Heart Failure and Chronic Obstructive Pulmonary Disease among Asians and Pacific Islanders in Hawai'i.

The objectives of the study were to compare ethnic differences in the rates of emergency department (ED) visits and hospitalizations, and to examine ethnic differences in how quickly patients with either chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) developed both diseases. A large health plan in Hawai.i provided administrative data (2007 to 2010) on patients of Native Hawaiian, Japanese, Chinese, Filipino, and White race/ethnicity. The study found distinct patterns of health risks among the multi-ethnic population of patients with COPD, CHF, or both conditions. Native Hawaiians had the highest rates of ED visits and hospitalizations. Japanese, the largest ethnic group and relatively low health risks, were selected as the reference population. In adjusted regression models, Filipino patients with CHF developed COPD the most rapidly; 71% faster than Japanese patients. Compared to Japanese, Native Hawaiians with COPD transitioned to CHF 68% faster. The study highlights ethnic disparities in adverse events and disease progression in patients with COPD and CHF, with important implications for clinical practice. Health care providers may want to inform patients of ways to mitigate the risks.

Epigallocatechin gallate suppresses Chlamydia pneumoniae mediated IgE responses in peripheral blood mononuclear cells: a pilot study.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) causes respiratory infection in children and adults and is associated with asthma and induction of immunoglobulin E (IgE) responses. Previous studies in our laboratory reported that green tea extract (GTE) and its catechin, epigallocatechin gallate (EGCG) have immunoregulatory effects on IgE responses. Whereas tea polyphenols have in vitro inhibitory effects on the proliferation of C. pneumoniae, the in vitro effects of EGCG on C. pneumoniae- mediated IgE responses haven't been studied. We sought to clarify the in vitro effect of EGCG on C. pneumoniae mediated IgE responses by peripheral blood mononuclear cells (PBMC) in asthma. METHODS: PBMC from subjects with asthma and non-asthmatic controls were incubated with C. pneumoniae and cultured for 10 days ±EGCG (0.5, 5.0, 50 ng/mL). IgE levels in supernatants were determined (ELISA). RESULTS: Elevated IgE levels were detected in supernatants of PBMC from an asthma patient (2.6 ng/mL), whereas IgE levels of PBMC from non-asthmatics were low (<2.0 ng/mL) at baseline. When EGCG (0.5-50 ng/mL) was added to PBMC from the asthma patient, IgE production was suppressed in a dose-dependent manner (10-30%), compared with no EGCG. When PBMC from the asthma patient were incubated with C. pneumoniae, IgE production was suppressed (70%); when PBMC from non-asthmatics were incubated with C. pneumoniae, IgE levels remained undetectable (<2.0 ng/mL). When EGCG (0.5-50 ng/mL) was added to PBMC from the asthma patient, C. pneumoniae-induced IgE production was suppressed moderately (35-48%). CONCLUSIONS: EGCG suppressed C. pneumoniae- mediated IgE responses in PBMC from a patient with asthma.

Cardiac Myosin Epitopes Recognized by Autoantibody in Acute and Convalescent Rheumatic Fever.

BACKGROUND: Acute rheumatic fever (ARF) is an autoimmune disorder associated with Streptococcus pyogenes infection. A prevailing hypothesis to account for this disease is that epitopes of self-antigens, such as cardiac myosin react to antibodies against S. pyogenes. The goal of our study was to confirm disease epitopes of cardiac myosin, identify immunodominant epitopes and to monitor the epitope response pattern in acute and convalescent rheumatic fever. METHODS: Enzyme-linked immunosorbant assays were used to determine epitopes immunodominant in acute disease and to track the immune response longitudinally to document any changes in the epitope pattern in convalescent sera. Multiplex fluorescence immunoassay was used to correlate anti-streptolysin O (ASO) and anti-human cardiac myosin antibodies. RESULTS: Disease-specific epitopes in rheumatic fever were identified as S2-1, 4 and 8. Epitopes S2-1, 4, 8 and 9 were found to be immunodominant in acute sera and S2-1, 8, 9, 29 and 30 in the convalescent sera. Frequency analysis showed that 50% of the ARF subjects responded to S2-8. S2-8 responders tended to maintain their epitope pattern throughout the convalescent period, whereas the S2-8 nonresponders tended to spread their responses to other epitopes later in the immune response. There was a significant correlation between anti-cardiac myosin and ASO titers. In addition, S2-8 responders showed elevated ASO titers compared with S2-8 non responders. CONCLUSION: Our studies confirm the existence of S2-1, 4 and 8 as disease-specific epitopes. We provide evidence that cardiac myosin S2-8 responders remain epitope stable in convalescence, whereas S2-8 nonresponders shift to neoepitopes. Multiplex data indicated a correlation between elevated ASO and anti-human cardiac myosin antibody titers. Mapping of cardiac myosin epitopes recognized in rheumatic fever sera may identify immunophenotypes of rheumatic fever.

Volcanic air pollution over the Island of Hawai'i: Emissions, dispersal, and composition. Association with respiratory symptoms and lung function in Hawai'i Island school children.

BACKGROUND: Kilauea Volcano on the Island of Hawai'i has erupted continuously since 1983, releasing approximately 300-12000metrictons per day of sulfur dioxide (SO2). SO2 interacts with water vapor to produce an acidic haze known locally as "vog". The combination of wind speed and direction, inversion layer height, and local terrain lead to heterogeneous and variable distribution of vog over the island, allowing study of respiratory effects associated with chronic vog exposure. OBJECTIVES: We characterized the distribution and composition of vog over the Island of Hawai'i, and tested the hypotheses that chronic vog exposure (SO2 and acid) is associated with increased asthma prevalence, respiratory symptoms, and reduced pulmonary function in Hawai'i Island schoolchildren. METHODS: We compiled data of volcanic emissions, wind speed, and wind direction over Hawai'i Island since 1992. Community-based researchers then measured 2- to 4-week integrated concentrations of SO2 and fine particulate mass and acidity in 4 exposure zones, from 2002 to 2005, when volcanic SO2 emissions averaged 1600metrictons per day. Concurrently, community researchers recruited schoolchildren in the 4th and 5th grades of 25 schools in the 4 vog exposure zones, to assess determinants of lung health, respiratory symptoms, and asthma prevalence. RESULTS: Environmental data suggested 4 different vog exposure zones with SO2, PM2.5, and particulate acid concentrations (mean±s.d.) as follows: 1) Low (0.3±0.2ppb, 2.5±1.2µg/m(3), 0.6±1.1nmolH+/m(3)), 2) Intermittent (1.6±1.8ppb, 2.8±1.5µg/m(3), 4.0±6.6nmolH+/m(3)), 3) Frequent (10.1±5.2ppb, 4.8±1.9µg/m(3), 4.3±6.7nmolH+/m(3)), and 4) Acid (1.2±0.4ppb, 7.2±2.3µg/m(3), 25.3±17.9nmolH+/m(3)). Participants (1957) in the 4 zones differed in race, prematurity, maternal smoking during pregnancy, environmental tobacco smoke exposure, presence of mold in the home, and physician-diagnosed asthma. Multivariable analysis showed an association between Acid vog exposure and cough and strongly suggested an association with FEV1/FVC <0.8, but not with diagnosis of asthma, or chronic persistent wheeze or bronchitis in the last 12months. CONCLUSIONS: Hawai'i Island's volcanic air pollution can be very acidic, but contains few co-contaminants originating from anthropogenic sources of air pollution. Chronic exposure to acid vog is associated with increased cough and possibly with reduced FEV1/FVC, but not with asthma or bronchitis. Further study is needed to better understand how volcanic air pollution interacts with host and environmental factors to affect respiratory symptoms, lung function, and lung growth, and to determine acute effects of episodes of increased emissions.

Impact of education on smoking cessation counseling by surgical residents.

BACKGROUND: Surgeons infrequently provide smoking cessation counseling for patients, in part because they lack training to do so. We investigated the efficacy of 2 methods of teaching smoking cessation counseling to surgical residents. METHODS: Residents' knowledge and attitude toward smoking cessation counseling were assessed by written test. Counseling skills were assessed with standardized patients. Residents were randomized for smoking cessation education: a "Role-play" group received a 1-hour lecture plus an hour of role-playing. An evidence-based medicine (EBM) group attended a 1- hour EBM journal club on related articles. Changes in residents' knowledge, attitude, and skills were assessed after education. RESULTS: Sixteen residents completed the study. After either form of education, residents demonstrated significant improvements in knowledge, attitude, and skills in smoking cessation counseling. There was no significant difference in improvement between the EBM and Role-play groups. CONCLUSIONS: A brief educational intervention can significantly improve residents' knowledge, attitude, and counseling skills for smoking cessation.

Report of the first annual Hawaii Asthma Research Consortium.

The first Hawaii Asthma Research Consortium was held on 7 May 2001 at Tripler Army Medical Center. Researchers investigating asthma-related problems and program directors of asthma projects were solicited statewide to present their projects. Ten lecturers focused on research and asthma projects in Hawaii in 20-minute presentations. An informal ten-minute discussion followed each presentation to encourage audience questions about the project and to discuss possible collaboration efforts between institutions. The institutions that were represented include: American Lung Association-Hawaii, Kaiser Permanente Center for Health Research Hawaii, Kapiolani Medical Center, Tripler Army Medical Center, University of Hawaii at Manoa, and Waianae Coast Comprehensive Health Center.

Aeroallergen sensitivity in Hawai'i: association with asthma and increased prevalence of sensitivity to indoor allergens since 1966.

Asthma and allergic diseases have increased globally. Earlier studies suggest a history of excess asthma morbidity and mortality in Hawai'i, with high prevalence of sensitization to outdoor aeroallergens among atopic children. This study was undertaken to test the hypotheses that specific allergens are more associated with asthma, and that sensitivity to common aeroallergens has increased in Hawai'i since 1966. Adult participants were recruited between 2001-2013, according to approved protocols. Data from 211 adults who reported physician-diagnosed asthma and 404 non-asthmatic controls are included in this analysis. Skin test responses to 8 common aeroallergens were assessed, and association between specific aeroallergen response and asthma diagnosis evaluated, using Chi-squared analysis. P-values < .05 were considered statistically significant. Compared to non-asthmatic controls, asthmatic participants were older, more likely to be of Mixed and non-White race, and more likely to be obese. Allergen sensitivity (atopy) was found in 85% of asthmatic and 72% of the controls. Prevalence (%) of positive responses to specific aeroallergens in asthmatic, non-asthmatic, and all atopic subjects, were: D. farinae (74, 59, 83), D. pteronyssinus (68, 52, 75), roach (42, 31, 46), cat (45, 19, 37), dog (27, 15, 25), grasses (34, 26, 37), weeds (22, 18, 25), and molds (18, 11, 17). Adjusted for age, race, and BMI, highest prevalence ratios [PR (95% CI)] were: D. farinae [1.16 (1.1-1.2)], D. pteronyssinus [1.16 (1.1-1.3)], cat [1.34 (1.2-1.5)], and dog [1.19 (1.1-1.3)]. This data indicates a strong association with asthma, and an increased prevalence in sensitivity to indoor allergens.

IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children.

Viral Hepatitis type B (HBV) is a public health concern, but has not been linked to asthma. Immunoglobulin (Ig) G is involved in HBV immune responses; less is known about IgE antibodies (Abs) against HBV in asthma. Given the importance of HBV, we sought to determine whether HBV vaccine contributes to asthma in children, by stimulating specific IgE production. Total IgE, IgE- or IgG-anti-HBVs Abs were studied in vaccinated pediatric asthmatics and non asthmatics. We found: (1) total IgE was higher in asthmatics; (2) total IgE did not correlate with IgE anti-HBVs; (3) IgE anti-HBVs did correlate with IgG-anti-HBVs in all subjects; (4)IgE- and IgG-HBVs Abs were similar in both groups; (5) IgE- or IgG anti-HBVs Abs did not correlate with age. Our findings indicate that HBV vaccination induces IgE responses in asthmatics and non asthmatics.

Is volcanic air pollution associated with decreased heart-rate variability?

OBJECTIVES: To determine the autonomic cardiovascular control among residents of Hawaii who are exposed to varying levels of volcanic air pollution (vog), which consists largely of sulfur dioxide (SO(2)) and acid aerosols. METHODS: In a cross-sectional study between April 2006 and June 2008, the authors measured cardiovagal autonomic function by heart-rate variability (HRV) in 72 healthy individuals who lived in four exposure zones on Hawaii Island: vog-free (n=18); episodic exposure to SO(2) >200 ppb and acid aerosol (n=19); chronic exposure to SO(2) ≥30 ppb and acid aerosol (n=15); and chronic exposure to acid aerosols (n=20). Individuals with diabetes or heart disease, or who had smoked in the preceding month were excluded. HRV was measured in all subjects during rest, paced breathing and active standing (Ewing manoeuvre). HRV was analysed in time and frequency domains and compared between the four exposure zones. RESULTS: There were no significant differences between exposure zones in HRV, in either time or frequency domains, even after adjustment for age, gender, ethnicity and body mass index. There was no significant HRV change in three individuals in whom HRV was measured before and during an exposure to combined SO(2) 100-250 ppb and concentration of respirable particles of diameter ≥2.5 µ (PM(2.5)) >500 µg/m(3). Age was significantly correlated with time-domain parameters during paced breathing and the Ewing manoeuvre. CONCLUSIONS: This study of healthy individuals found no appreciable effects of vog on the autonomic nervous system.

Down-regulation of caveolin-1, an inhibitor of transforming growth factor-beta signaling, in acute allergen-induced airway remodeling.

Asthma can progress to subepithelial airway fibrosis, mediated in large part by transforming growth factor-beta (TGF-beta). The scaffolding protein caveolin-1 (cav1) can inhibit the activity of TGF-beta, perhaps by forming membrane invaginations that enfold TGF-beta receptors. The study goals were 1) to evaluate how allergen challenge affects lung expression of cav1 and the density of caveolae in vivo 2) to determine whether reduced cav1 expression is mediated by interleukin (IL)-4 and 3) to measure the effects of decreased expression of cav1 on TGF-beta signaling. C57BL/6J, IL-4-deficient mice, and cav1-deficient mice, sensitized by intraperitoneal injections of phosphate-buffered saline or ovalbumin (OVA) at days 0 and 12, received intranasal phosphate-buffered saline or OVA challenges at days 24, 26, and 28. Additionally, another group of C57BL/6J mice received IL-4 by intratracheal instillation for 7 days. We confirmed that the OVA-allergen challenge increased eosinophilia and T-helper type 2-related cytokine levels (IL-4, IL-5, and IL-13) in bronchoalveolar lavage. Allergen challenge reduced lung cav1 mRNA abundance by 40%, cav1 protein by 30%, and the number of lung fibroblast caveolae by 50%. Administration of IL-4 in vivo also substantially decreased cav1 expression. In contrast, the allergen challenge did not decrease cav1 expression in IL-4-deficient mice. The reduced expression of cav1 was associated with activation of TGF-beta signaling that was further enhanced in OVA-sensitized and challenged cav1-deficient mice. This study demonstrates a previously unknown modulation of TGF-beta signaling by IL-4, via cav1, suggesting novel therapeutic targets for controlling the effects of TGF-beta and thereby ameliorating pathological airway remodeling.