Increased Airway Obstruction Research Articles

Air pollution exposure and lung function until age 16 years: the PIAMA birth cohort study.

Evidence for the effects of air pollution exposure on lung function growth into adolescence is scarce. We investigated associations of air pollution exposure with lung function and lung function growth until age 16.We conducted both longitudinal (n=915) and cross-sectional (n=721) analyses of associations of air pollution exposure with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) growth from ages eight to 16 and FEV1 and FVC at age 16. We estimated residential concentrations of nitrogen dioxide (NO2), "soot" and particulate matter (PMx, where x is the 50% cut-off aerodynamic diameter in µm) with diameters of <2.5 µm (PM2.5), <10 µm (PM10) and 2.5-10 µm (PMcoarse) during the preschool, primary school and secondary school time windows by land use regression models. Associations with (growth in) FEV1 and FVC were analysed by linear (mixed effects) regression.Higher air pollution exposure was associated with reduced FEV1 growth (e.g. adjusted difference -0.26% (95% CI -0.49 to -0.03%) per interquartile range increase in secondary school PM2.5) and lower FEV1 (adjusted difference -2.36% (95% CI -3.76 to -0.94%)), but was not adversely associated with FVC. Associations with FEV1 were stronger in boys than girls and were not modified by asthma status.Higher air pollution exposure may lead to increased airway obstruction, but not reduced lung volume in adolescence.

Exposure to Environmental Contaminants and Lung Function in Adolescents-Is There a Link?

Dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDF)), polychlorinated biphenyls (PCBs), and brominated flame retardants (BDEs) are well known toxic environmental contaminants. Their possible role in the incidence of respiratory disease is not yet well understood. Previous studies showed a negative effect on lung function in relation to prenatal and lactational dioxin exposure in pre-pubertal children. Effects of BDE exposure on the lung function have not previously been evaluated. As part of a longitudinal cohort study, the effects of perinatal dioxin (PCDD/F) exposure and serum PCDD/F, dl-PCB, and BDE levels on lung function in adolescents were assessed using spirometry, a body box, and diffusion measurements. Thirty-three children (born between 1986 and 1991) consented to the current follow-up study. Prenatal, lactational, and current dioxin, PCB, and BDE concentrations were determined using GC-MS. No relationship was seen between prenatal and lactational dioxin exposure, nor with current PCB body burden, and lung function. Indications of increasing airway obstruction were seen in relation to increasing current BDE exposure. This is a novel finding and certainly warrants further research.

Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 Against Respiratory Syncytial Virus and Human Metapneumovirus Infections.

The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant–antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression. The objective of the current study was to establish the role of Nrf2 in shaping innate immune responses, clinical disease, airway inflammation, and viral replication in established experimental models of intranasal RSV and human metapneumovirus (hMPV) infections, by employing mice genetically deficient for the Nrf2 gene. Compared to control wild type (WT), mice genetically deficient in Nrf2 (Nrf2 KO) developed enhanced clinical disease, airway inflammation and pathology, and significantly greater lung viral titers following experimental infection with either RSV or hMPV. In particular, compared to control mice, RSV-infected Nrf2 KO mice lost more body weight and had increased airway obstruction at time points characterized by a remarkable increase in inflammatory cytokines and airway neutrophilia. Airway levels of AOEs and enzymes that regulate synthesis of the endogenous hydrogen sulfide (H2S) pathway, which we showed to play an important antiviral function, were also decreased in RSV-infected Nrf2 KO compared to WT. In conclusion, these results suggest that Nrf2 is a critical regulator of innate, inflammatory, and disease-associated responses in the airways of mice infected with viruses that are members of the Pneumoviridae family. Importantly, the results of this study suggest that Nrf2-dependent genes, including those controlling the cellular antioxidant and H2S-generating enzymes and cytokines can affect several aspects of the antiviral response, such as airway neutrophilia, clinical disease, airway obstruction, and viral replication.

Enhancing our understanding of computerised adventitious respiratory sounds in different COPD phases and healthy people.

Timely diagnosis of acute exacerbations of COPD (AECOPD) is challenging as it depends on patients' reports. AECOPD are characterised by increased airway obstruction, mucus and air trapping, which results in changes in lung acoustics. Thus, adventitious respiratory sounds (ARS) may be useful to detect/monitor AECOPD. To evaluate computerised ARS changes during AECOPD. 25 non-hospitalised patients with AECOPD (16♂, 70 [62.5-77.0]yrs, FEV1 59 [31.5-73.0]%predicted) and 34 healthy volunteers (17♂, 63.5 [57.7-72.3]yrs, FEV1 103.0 [88.8-125.3]%predicted) were enrolled. ARS at anterior and posterior right and left chest were recorded at hospital presentation (T1), 15 days (T2) and 45 days (T3) after hospital presentation from patients with AECOPD and only once from healthy participants. A subsample of 9 patients (7♂; 66 [60.0-76.0]yrs; FEV1 62 [26.5-74.0]%predicted) was also included to study ARS pre-AECOPD (T0). Number of crackles and wheeze occupation rate (%Wh) were processed using validated algorithms. During AECOPD, patients presented more inspiratory crackles at T1 than T3 (p = 0.013) and more inspiratory %Wh at T1 than T2 (p = 0.006), at posterior chest. Patients with stable COPD presented more inspiratory crackles (p = 0.012), at posterior chest, and more expiratory %Wh, both at anterior (p < 0.001) and posterior (p = 0.001) chest, than healthy participants. No differences were observed for the remaining ARS parameters or subsamples (p > 0.05). Inspiratory crackles seem to persist until 15 days post exacerbation whilst inspiratory %Wh decreased after this period. ARS seem to be sensitive to monitor AECOPD. This information may allow advances in monitoring the recovery time of patients with AECOPD across all clinical and non-clinical settings.

Periodontal health status and lung function in two Norwegian cohorts.

Rationale and objectivesThe oral cavity is united with the airways, and thus poor oral health may affect respiratory health. However, data on the interaction of periodontal and respiratory health is limited. We aimed to evaluate whether periodontal health status, assessed by the Community Periodontal Index (CPI), was related to lung function among young and middle-aged adults in two Norwegian cohorts.MethodsPeriodontal health status and lung function were measured among 656 participants in the Norwegian part of the European Community Respiratory Health Survey (ECHRS III) and the RHINESSA offspring study. Each participant was given a CPI-index from 0 to 4 where higher values reflect poorer periodontal status. The association between CPI and lung function was estimated with linear regression adjusting for age, gender, smoking, body mass index, exercise, education, use of antibiotics, inhaled medication and corrected for clustering within families.Main resultsParticipants with CPI 3–4 had significantly lower FEV1/FVC ratio compared to participants with CPI 0, b (95% CI) = -0.032 (-0.055, -0.009). Poorer periodontal health was associated with a significant decrease in the FEV1/FVC ratio with an adjusted regression coefficient for linear trend b (95% CI) = -0.009 (-0.015, -0.004) per unit increase in CPI. This negative association remained when excluding asthmatics and smokers (-0.014 (-0.022, -0,006)).ConclusionsPoorer periodontal health was associated with increasing airways obstruction in a relatively young, healthy population. The oral cavity is united with the airways and our findings indicate an opportunity to influence respiratory health by improving oral health.

Association between the Serum Metabolic Profile and Lung Function in Chronic Obstructive Pulmonary Disease.

Although dietary patterns are known to modulate disease severity in patients with chronic obstructive pulmonary disease (COPD), the relationship between the circulating lipid profile and lung function in COPD has not been studied extensively. There were 43 COPD patients with a history of smoking and 39 patients with a history of biomass fuel exposure recruited in this study, along with 43 age-matched healthy controls. All participants underwent complete lung function profiling, and their glucose and lipid profiles were measured. The association between the metabolic profile and lung function was assessed using the Spearman's rank-order correlation coefficient. 52.4% of the COPD patients were smokers compared to the healthy group (46.5%). We found an inverse correlation between triglyceride and functional residual capacity (p=-0.21, p=0.05) and a positive association between serum cholesterol and overall airway resistance (R5) (p=0.24, p=0.04) and central airway resistance (R20) (p=0.32, p=0.004). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) ratio and LDL/HDL ratio were also found to correlate with R5 (p=0.25, 0.23, and 0.22, respectively) and R20 (p=0.31, 0.24, and 0.24, respectively). No significant association was observed between other metabolites and either spirometric or plethysmographic lung function indices. High serum triglyceride and cholesterol may increase the resistance in the airways, which may lead to increased airway obstruction. Therefore, monitoring of lipid profile should be considered in the diagnosis and management of COPD.

Comparative Clinical, Physiological, and Inflammatory Characteristics of Elderly Subjects With or Without Asthma and Young Subjects With Asthma

Asthma seems to present in the elderly as a specific phenotype that remains to be further described. In this prospective observational study, we aimed to assess the multidimensional aspects of asthma in the elderly. In young (18 to 35 years old) subjects with mild to moderate asthma and elderly subjects (aged≥60 years) either with or without mild to moderate asthma, we compared asthma control, health care and medication use, lung function, markers of airway and systemic inflammation, and adherence to therapy. Fifty subjects were recruited in each group. Elderly people with asthma showed more marked airway obstruction compared with young people with asthma and elderly people without asthma. They also had poorer asthma control, mainly associated with a lower FEV1, compared with young people with asthma, although airway responsiveness, health care use, prescribed doses of inhaled corticosteroids, and adherence to treatment were similar in both groups. Elderly subjects had an increase in some markers of systemic inflammation and bronchial epithelial dysfunction compared with young people with asthma. Blood eosinophils were higher in both asthma groups, particularly in elderly people with asthma. Sputum neutrophils were increased in both groups of elderly subjects and sputum eosinophils were increased in elderly people with asthma compared with the other two groups. Asthma in the elderly presents as a specific phenotype associated with increased airway obstruction and mixed airway inflammation in addition to signs of systemic inflammation.

Mechanisms of ECG signs in chronic obstructive pulmonary disease

ObjectivePatients with chronic obstructive pulmonary disease (COPD) often have abnormal ECGs. Our aim was to separate the effects on ECG by airway obstruction, emphysema and right ventricular (RV) afterload in...

Serum Vitamin D levels in Chronic Obstructive Pulmonary Disease

Introduction: Lower serum 25 (0H) Vitamin D is associated with decreased lung function in healthy population and various lung disease. Information on the relationship of levels of serum 25 (OH) Vitamin D with severity of Chronic Obstructive Pulmonary Disease (COPD) is important in standardizing the treatment, in planning appropriate follow up and improving quality of life. This study also warranted further trial to assess the effect of serum 25 (OH) vitamin D on morbidity and mortality in COPD patients. Material and Methods: It was a prospective (observational), cross-sectional study which included all patients with Chronic Obstructive Pulmonary Disease (COPD) attended the Department of Pulmonary Medicine, People’s College of Medical Sciences &amp; RC, Bhopal, over a period of 1 year 6 months. Results: The mean serum 25 (OH) vitamin D level in COPD patients was 27.86±16.47 ng/ml. There was no significant difference in serum 25 (OH) vitamin D between patients in different age groups. The serum 25 (OH) vitamin D levels varied significantly between different GOLD stages and different mMRC dyspnea grades. The patient who had a history of admission for twice or more in the past 1 year had a lower mean serum 25 (OH) vitamin D level as compared to patient with just one or no hospitalization in the past. Conclusion: Decrease serum 25(0H) vitamin D levels were associated with increase airway obstruction.

Expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease with a cold-dryness symptom pattern

OBJECTIVETo reveal the effects on expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease (COPD) and a cold-dryness symptom pattern induced by elastase and smoking. METHODSThe COPD model was established with an elastase dose into the trachea combined with exposure to smoking; the COPD model cold-dryness symptom pattern was further developed by exposure to a cold, dry environment. After 90 days, pathologic lung sections, inflammatory cytokine levels (measured by enzyme linked immunosorbent assay), mRNA and protein expression of mucus-associated proteins and aquaporins (measured by real-time polymerase chain reaction and western blots) were examined. RESULTSCytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in the COPD and the cold-dryness symptom pattern COPD groups were all significantly higher than in controls (each P < 0.01). IL-6 and IL-8 levels were higher in the cold-dryness symptom pattern COPD group than in the COPD group (each P < 0.05). The AQP5 mRNA expression in the cold-dryness symptom pattern COPD and COPD groups was lower than in the control group (P < 0.01), and that in the cold-dryness symptom pattern COPD group was lower than the COPD group (P < 0.05). The expression of MUC5AC and MUC5B mRNAs in the cold-dryness symptom pattern COPD group and COPD group was higher than in the control group (each P < 0.01), and that in the cold-dryness symptom pattern COPD group was higher than the COPD group (P < 0.01, and P < 0.05, respectively). The ratio of MUC5AC mRNA/MUC5B mRNA was COPD group < the cold-dryness symptom pattern COPD group < the control group. AQP4 and AQP5 protein expression in the cold-dryness symptom pattern COPD group was lower than that in the COPD group which was lower again than in the control group. MUC5AC and MUC5B expression in the cold-dryness symptom pattern COPD group was higher than in the COPD group and higher again than in the control group. CONCLUSIONSCold-dryness affects the expression of mucus-associated protein mRNA and its corresponding proteins, reducing the secretion of aquaporins and increasing the secretion of mucins. Imbalance in aquaporins and mucins can affect the function of mucus, increasing airway obstruction.

Increasing airway obstruction from 8 to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era

BackgroundThe evolution of airway obstruction into late adolescence of extremely preterm (gestational age <28 weeks) or extremely low-birthweight (birth weight <1000 g) survivors in the era after surfactant was introduced...

Peak oxygen uptake and breathing pattern in COPD patients--a four-year longitudinal study.

BackgroundActivities of daily living in patients with chronic obstructive pulmonary disease (COPD) are limited by exertional dyspnea and reduced exercise capacity. The aims of the study were to examine longitudinal changes in peak oxygen uptake (V̇O2peak), peak minute ventilation (V̇Epeak) and breathing pattern over four years in a group of COPD patients, and to examine potential explanatory variables of change.MethodsThis longitudinal study included 63 COPD patients, aged 44-75 years, with a mean forced expiratory volume in one second (FEV1) at baseline of 51 % of predicted (SD = 14). The patients performed two cardiopulmonary exercise tests (CPETs) on treadmill 4.5 years apart. The relationship between changes in V̇O2peak and V̇Epeak and possible explanatory variables, including dynamic lung volumes and inspiratory capacity (IC), were analysed by multivariate linear regression analysis. The breathing pattern in terms of the relationship between minute ventilation (V̇E) and tidal volume (VT) was described by a quadratic equation, VT = a + b∙V̇E + c∙V̇E2, for each test. The VTmax was calculated from the individual quadratic relationships, and was the point where the first derivative of the quadratic equation was zero. The mean changes in the curve parameters (CPET2 minus CPET1) and VTmax were analysed by bivariate and multivariate linear regression analyses with age, sex, height, changes in weight, lung function, IC and inspiratory reserve volume as possible explanatory variables.ResultsSignificant reductions in V̇O2peak (p < 0.001) and V̇Epeak (p < 0.001) were related to a decrease in resting IC and in FEV1. Persistent smoking contributed to the reduction in V̇O2peak. The breathing pattern changed towards a lower VT at a given V̇E and was related to the reduction in FEV1.ConclusionIncreasing static hyperinflation and increasing airway obstruction were related to a reduction in exercise capacity. The breathing pattern changed towards more shallow breathing, and was related to increasing airway obstruction.

Airway Obstruction Worsens in Young Adults with Asthma Who Become Obese

Few studies have examined how developing obesity in early adulthood affects the course of asthma. We analyzed lung function and asthma impairment and risk among nonobese children with asthma, comparing those who were obese in young adulthood with those who remained nonobese. We carried out the post hoc analysis of 771 subjects with mild to moderate asthma who were not obese (pediatric definition, body mass index [BMI] < 95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5-12 years. The subjects were then followed to age 20 years or more. For visits at ages 20 years or more, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were nonobese at all visits and 151 who were obese (adult definition of BMI ≥ 30 kg/m(2)) on at least 1 visit (median number of visits when obese = 4, IQR 2-7). Compared with participants who were nonobese (BMI 23.4 ± 2.6 kg/m(2)), those who became obese (BMI 31.5 ± 3.8 kg/m(2)) had significant decreases in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (P < .0003) and FEV1 (P = .001), without differences in FVC (P = .15) during visits at ages 20 years or more. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (P = .0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the 2 groups. Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

Bradykinin and capsaicin induced airways obstruction in the guinea pig are platelet dependent

IntroductionAirways obstruction induced by intravenously administered bradykinin is abolished in guinea pigs treated with indomethacin, which has been shown to be, at least in part thromboxane dependent. As thromboxane is primarily generated from circulating platelets, we investigated whether airways obstruction induced by bradykinin, and other spasmogens, is platelet dependent and the role platelet aggregation played in this response. MethodsGuinea pigs were chronically treated with busulfan to induce thrombocytopenia. Total lung resistance was measured in anaesthetised and mechanically ventilated control and thrombocytopaenic animals to various stimuli that induce airways obstruction. In other experiments, platelet aggregation was assessed in vitro in response to the same stimuli: guinea pigs were anaesthetized, blood was collected and centrifuged to generate firstly platelet-rich plasma and then platelet-poor plasma. Platelets were resuspended in HEPES buffer and platelet aggregation was assessed. ResultsBusulfan treatment significantly reduced the number of circulating platelets in guinea-pigs by 85.5%, but had no significant effect on the number of circulating leukocytes. Treatment with busulfan had no significant effect on bronchoconstriction induced by the direct acting spasmogens histamine or methacholine. However, platelet depletion significantly increased airways obstruction induced by Substance P, but caused a significant reduction in airways obstruction induced by bradykinin, bombesin or capsaicin (P < 0.05). None of these stimuli however were able to exhibit a direct effect on platelet aggregation in vitro. Moreover, busulfan did not significantly alter the contractility of guinea-pig isolated trachea in response to capsaicin. ConclusionAirways obstruction induced by bombesin, capsaicin and bradykinin is platelet dependent, but not secondary to platelet aggregation.

O-110 Effect Of Preterm Birth On Adulthood Lung Function: Finnish Birth Registry And Clinical Follow-up Study

<h3>Background</h3> Preterm birth and maternal gestational disorders may adversely impact the pulmonary health of offspring. <h3>Aims</h3> To examine whether exposure to common conditions during fetal-life (preterm birth, gestational hypertension, gestational diabetes) predicts poorer lung function in young adults. <h3>Methods</h3> The ESTER study is a case-control cohort study of individuals born in Northern Finland 1985–89. Study design has two parts: 1) preterm birth included 139 early preterm (&lt;34 weeks) and 239 late preterm (34- &lt;37 weeks) birth subjects; 2) maternal pregnancy disorder included 154 subjects exposed to maternal gestational diabetes (GDM), 136 to pre-eclampsia (PE) and 179 to gestational hypertension (GH). Control group sizes varied. At mean age of 23.5y (±1.7), participants underwent a detailed clinical study including spirometric measurement of FVC, FEV1 and FEV/FVC%, as % from predicted. <h3>Results</h3> Participants born preterm had similar FVC but poorer airflow than term-born. This difference was seen among early and late preterm births (Table1), although for the late preterm, significant only in preliminary models. Lung function in individuals exposed to PE was lower, but this difference disappeared by adjusting for gestational length. Maternal GH or GDM were unrelated to lung function (Table 2). <h3>Conclusion</h3> Shorter gestation and fetal-life conditions are likely to have long-lasting impacts on lung function: preterm-born individuals are likely to experience increased airway obstruction. Even late preterm birth (majority of preterm births), can increase the risk of poor pulmonary outcome. Preeclampsia may have similar effects, adding to the fetal origins of poor pulmonary health. This could be counterbalanced by physical excercise.

Airways obstruction and pulmonary capillary blood volume in children with sickle cell disease

SummaryObjectives and Working Hypothesis Airways obstruction occurs in young children with sickle cell disease (SCD). Our aim was to test the hypothesis that increased pulmonary capillary blood volume at least in part explained the increased airways obstruction as this would inform which therapy might be most appropriate to treat the airway obstruction. Study design Observational study. Patient-subject selection Twenty-five SCD children and 25 ethnic origin matched controls were recruited. Methodology Respiratory system resistance, using impulse oscillometry at 5 Hz (R5 %pred), pulmonary capillary blood volume (Vc), alveolar volume (VA), and spirometry were assessed before and after bronchodilator (ipratropium bromide). Lung volume measurements were also made. Results The SCD children compared to the controls had a higher R5 %pred before (median 133 (range 88–181)% vs. 102 (83–184)%, P = 0.0046) and after (105 (79–150)% vs. 91 (64–147)%, P = 0.0489) bronchodilator and their median Vc/VA (ml/L) was higher before (26 (18–38) vs. 18 (14–28) P < 0.0001) and after (26 (19–41) vs. 18 (13–27) P < 0.0001) bronchodilator. There were similar decreases in R5 %pred post-bronchodilator in the two groups, but no significant changes in Vc/VA in either group. Vc/VA correlated significantly with R5 %pred in the SCD children only. Conclusions Increased pulmonary capillary blood volume contributes to the increased airways obstruction in children with SCD, hence, bronchodilators may be of limited benefit in reducing their airways obstruction. Pediatr Pulmonol. 2014; 49:716–722. © 2013 Wiley Periodicals, Inc.

Airways obstruction and pulmonary capillary blood volume in children with sickle cell disease

Airways obstruction occurs in young children with sickle cell disease (SCD). Our aim was to test the hypothesis that increased pulmonary capillary blood volume at least in part explained the increased airways obstruction as this would inform which therapy might be most appropriate to treat the airway obstruction. Observational study. Twenty-five SCD children and 25 ethnic origin matched controls were recruited. Respiratory system resistance, using impulse oscillometry at 5 Hz (R5 %pred), pulmonary capillary blood volume (Vc), alveolar volume (VA), and spirometry were assessed before and after bronchodilator (ipratropium bromide). Lung volume measurements were also made. The SCD children compared to the controls had a higher R5 %pred before (median 133 (range 88-181)% vs. 102 (83-184)%, P = 0.0046) and after (105 (79-150)% vs. 91 (64-147)%, P = 0.0489) bronchodilator and their median Vc/VA (ml/L) was higher before (26 (18-38) vs. 18 (14-28) P < 0.0001) and after (26 (19-41) vs. 18 (13-27) P < 0.0001) bronchodilator. There were similar decreases in R5 %pred post-bronchodilator in the two groups, but no significant changes in Vc/VA in either group. Vc/VA correlated significantly with R5 %pred in the SCD children only. Increased pulmonary capillary blood volume contributes to the increased airways obstruction in children with SCD, hence, bronchodilators may be of limited benefit in reducing their airways obstruction.

Effects of high altitude and cold air exposure on airway inflammation in patients with asthma

AimsEighteen patients with asthma were evaluated during preparation to climb to extreme altitude in order to study the effects of low fractional inspired oxygen (FiO2), prolonged exposure to cold air...

γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations.

Most asthma exacerbations are triggered by virus infections, the majority being caused by human rhinoviruses (RV). In mouse models, γδT cells have been previously demonstrated to influence allergen-driven airways hyper-reactivity (AHR) and can have antiviral activity, implicating them as prime candidates in the pathogenesis of asthma exacerbations. To explore this, we have used human and mouse models of experimental RV-induced asthma exacerbations to examine γδT-cell responses and determine their role in the immune response and associated airways disease. In humans, airway γδT-cell numbers were increased in asthmatic vs. healthy control subjects during experimental infection. Airway and blood γδT-cell numbers were associated with increased airways obstruction and AHR. Airway γδT-cell number was also positively correlated with bronchoalveolar lavage (BAL) virus load and BAL eosinophils and lymphocytes during RV infection. Consistent with our observations of RV-induced asthma exacerbations in humans, infection of mice with allergic airways inflammation increased lung γδT-cell number and activation. Inhibiting γδT-cell responses using anti-γδTCR (anti-γδT-cell receptor) antibody treatment in the mouse asthma exacerbation model increased AHR and airway T helper type 2 cell recruitment and eosinophilia, providing evidence that γδT cells are negative regulators of airways inflammation and disease in RV-induced asthma exacerbations.

Inhibitors of Phosphoinositol 3 Kinase and NF&amp;#954;B for the Treatment of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.