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Purpose of Review: The term 'airway remodeling' reflects changes in the type, quantity, and nature of airway wall components and their organization. The purpose of this review is to look at recent publications on airway remodeling in asthma., Recent Findings: Animal models and in-vitro studies have confirmed the involvement of airway epithelium, airway smooth muscle (ASM), and extracellular matrix components in asthma-related airway remodeling. They report influences on proliferation of ASM cells, and how their orientation or morphology, in addition to the heterogeneity of ASM mass at different levels of airways could influence their effects. Clinical benefits have been observed following reduction of ASM following bronchial thermoplasty. Asthmatic epithelial cell transcriptome alterations were found to involve metabolism and epigenetics, beyond epithelial mesenchymal trophic unit driven by injury and repair in chronic inflammation. New ways to explore airway remodeling such as imaging or endoscopic techniques have been evaluated. Finally, new data support the role of eosinophils and mast cells in remodeling and show the influence of new asthma drugs on this process., Summary: As recently stated by an American Thoracic Society task force, we need more research on airway remodeling, its determinants and clinical relevance, and on the effects of asthma drugs on its various components.

Background: 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., Methods: 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., Results: 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 FEV 1 , 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., Conclusions: 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., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Airway disorders are common in regular chlorinated swimming pool attendees, particularly competitive athletes, but the impact of intense swimming training on airway function and structure remains unclear., Objective: This study aimed to evaluate airway inflammation and remodeling in elite swimmers., Methods: Twenty-three elite swimmers were tested during off-training season. All had exhaled nitric oxide measurement, methacholine test, eucapnic voluntary hyperpnea challenge, allergy skin prick tests, and bronchoscopy with bronchial biopsies. Clinical data and tissues from 10 age-matched mild-asthmatic and 10 healthy nonallergic subjects were used for comparison., Results: Swimmers had increased airway mucosa eosinophil and mast cell counts than did controls (P < .05). They had more goblet cell hyperplasia and higher mucin expression than did healthy or asthmatic subjects (P < .05). A greater submucosal type I and III collagen expression and tenascin deposition was also observed in swimmers than in controls (P < .05). Neither exhaled nitric oxide nor airway responsiveness to methacholine or eucapnic voluntary hyperpnea challenge correlated with these inflammatory and remodeling changes., Conclusion: Intense, long-term swimming training in indoor chlorinated swimming pools is associated with airway changes similar to those seen in mild asthma, but with higher mucin expression. These changes were independent from airway hyperresponsiveness. The long-term physiological and clinical consequences of these changes remain to be clarified., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Purpose: Obesity is associated with changes in pulmonary function and increased systemic inflammation. We explored the relationships among adiposity, body fat distribution indices, serum inflammatory markers and pulmonary function., Methods: This was a post-hoc cross-sectional analysis that included subjects who had previously participated in randomized studies on obesity at our centre. Non-smoking sedentary men (282 subjects, mean age 42) without respiratory diseases were studied. BMI, waist circumference (WC), visceral and subcutaneous adipose tissue (AT), lung residual volume (RV), vital capacity (VC) and expiratory reserve volume (ERV) were measured. Serum leptin, adiponectin, tumor necrosis factor alpha (TNF-α) and high-sensitive C-reactive protein (hs-CRP) levels were measured., Results: In subjects with metabolic syndrome (n=124), percent predicted ERV and RV were significantly associated with BMI (ERV: r=-0.19, p=0.02, RV: r=-0.28, p=0.0007), WC (r=-0.20, p=0.02, r=-0.26, p=0.002), visceral (r=-0.22, p=0.007, r=-0.25, p=0.002) and subcutaneous AT (r=-0.19, p=0.02, r=-0.28, p=0.0007). Percent predicted VC correlated with visceral (r=-0.20, p=0.02) and subcutaneous AT (r=-0.18, p=0.03). Leptin was strongly correlated with BMI (MS/no-MS: r=0.52, p=0.0005/r=0.62, p < 0.0001), WC (r=0.41, p=0.008/r=0.49, p < 0.0001), visceral (r=0.27,p=0.09/0.43, p < 0.0001) and subcutaneous AT (r=0.46, p=0.003/r=0.66, p < 0.0001), while adiponectin levels were associated in subjects with no-MS with WC (r=-0.20, p=0.01), visceral (r=-0.22, p=0.008), and subcutaneous AT (r=-0.17, p=0.05). When adjusted for anthropometric measures, neither ERV, RV nor VC was significantly correlated with serum leptin, adiponectin, TNF-α, or hs-CRP levels., Conclusion: These results suggest that the influence of obesity on lung function in healthy subjects is mostly mediated by mechanical factors. Furthermore, not only BMI but also the pattern of fat distribution should be considered when studying associations between adiposity indices and mechanical or inflammatory variables potentially associated with pulmonary function.

Purpose: There is an increased prevalence of asthma and airway hyperresponsiveness in elite athletes, particularly in swimmers. High intensity exercise may induce airway inflammation and subsequent remodelling in these subjects. Our aim was to evaluate the effects of high-intensity training on induced-sputum cell populations in elite athletes., Methods: Swimmers and runners with hyperresponsive airways (SH and RH), defined by a provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20) <16 mg/ml or with normoresponsive airways (PC20 > 16 mg/ml; SN, RN) to methacholine were enrolled. The mean PC20 was 2.27 mg/ml in SH (n=12), 32.2 in SN (n=10), 3.25 in RH (n=10) and 41.5 in RN (n=13). All athletes had two induced sputum analyses at one- to two-week intervals in random order: after a period of 72 hours without training, 24 hours after a training session., Results: PC20 was unchanged after training. The median % neutrophils and eosinophils in groups SH, SN, RH, and RN, respectively, were 26.5-1.6, 8.6-0.3, 28.0-0.03 and 25.5-0.1 before and 45.0-0.5, 31.1-0.4, 54.0-0.6 and 48.3-0.3 after training. While the magnitude of the increase in neutrophils was similar for all groups, it reached statistical significance (pre-post-training) only in the SH group (P = 0.039)., Conclusion: A one-hour session of high-intensity training was associated with an increase in airway neutrophils among hyperresponsive swimmer athletes, while airway responsiveness remained unchanged in all groups.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) affects a significant number of asthmatic patients and is notably associated with a more difficult‐to‐control asthma and marked inflammation. We need more studies on this specific asthma phenotype and its possible subphenotypes, in order to better individualize treatments. Aim: The aim of this study is to identify and characterize subphenotypes of asthma patients with CRSwNP using clinical, physiological and inflammatory variables. Methods: K‐means cluster analysis was performed on 17 clinical, physiological, and inflammatory variables from 1263 patients of all asthma severity and on a subpopulation of patients with asthma and CRSwNP. Study was registered on ClinicalTrials.gov (NCT 03694847). Results: On the overall population, three groups were identified. Cluster T1 (n = 708) are young, have a short asthma duration and a low prevalence of CRSwNP. Cluster T2 (n = 263) have the longest asthma duration and Cluster T3 (n = 292) are older with the shortest asthma duration. Patients in Clusters T2 and T3 have similar prevalences of CRSwNP. On the subpopulation of asthma with CRSwNP, three clusters were also identified. Cluster S1 (n = 83) have mild‐to‐moderate asthma with normal lung function. Clusters S2 (N = 53) and S3 (N = 42) include patients with severe asthma and decreased lung function, but those in Cluster S2 have a longer asthma duration, whereas those Cluster S3 have late‐onset asthma. Conclusions: Despite coexistence of asthma and CRSwNP, not all patients have the same evolution of their asthma. Different phenotypes of asthma with CRSwNP can be identified and exploration of the characteristics of these subgroups could lead to a better individualized, targeted management. [ABSTRACT FROM AUTHOR]

Skiers and swimmers present characteristics of airway inflammation and remodelling of the extracellular matrix similar to what is observed in mild asthma. We aimed to compare serum and sputum MMP-9/TIMP-1 levels, to assess the balance between airway fibrogenesis and inflammation process in both categories of athletes, and to observe its seasonal variations in winter sports athletes. We conducted a retrospective study. Winter sports athletes (n = 41), swimmers (n = 25) and healthy nonathletes (n = 10) had blood sampling, lung function measurement, skin prick tests, eucapnic voluntary hyperpnoea challenge, methacholine inhalation test, and induced sputum analysis. Twelve winter sport athletes performed the tests during both summer and winter. Serum and sputum biomarkers were measured by ELISA. No significant difference in serum or sputum MMP-9/TIMP-1 ratio was observed between groups, nor relationship with airway function or responsiveness. Serum MMP-9/TIMP-1 ratio was higher during the summer in winter sport athletes compared with winter season (median [Interquartile range]: 3.65 [2.47-4.03] ng.ml−1 and 1.27 [0.97-1.62] ng.ml−1, respectively, p = 0.005). Sputum MMP-9 correlated with methacholine PC20 (r = 0.45, p = 0.019) and serum cc16/SP-D ratio (r = −0.47, p = 0.013). MMP-9/TIMP-1 ratio in sputum or serum may fluctuate with training or environment but does not correlate with airway function or responsiveness in athletes. [ABSTRACT FROM AUTHOR]

Abstract Background Phosphodiesterase 4 (PDE4) inhibitors increase intracellular cyclic adenosine monophosphate (cAMP), leading to regulation of inflammatory cell functions. Roflumilast is a potent and targeted PDE4 inhibitor. The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge. Methods 25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15. Results Roflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen. Conclusions This study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR. Trial Registration ClinicalTrials.gov: NCT01365533

Background: The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. Objective: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. Methods: We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with <5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. Results: Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. Conclusions: Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes. [ABSTRACT FROM AUTHOR]

The development of COPD features, such as an incomplete reversibility of airway obstruction (IRAO), in smoking or non-smoking asthmatic patients, a condition often named Asthma-COPD Overlap (ACO), has been recognized for decades. However, there is a need to know more about the sub-phenotypes of this condition according to smoking. This study aimed at comparing the clinical, physiological and inflammatory features of smoking and non-smoking asthmatic patients exhibiting IRAO. In this cross-sectional study, patients with an IRAO with (ACO, ≥20 pack-years) or without (NS-IRAO, <5 pack-years) significant smoking history completed questionnaires about asthma control (ACQ, score 0-6, 6 = better score) and quality of life (AQLQ, score 1-7, 1 = better score) and performed expiratory flows, lung volume and carbon monoxide diffusion capacity measurements. Blood sampling and induced sputum were obtained for systemic and lower airway inflammation assessment. A total of 115 asthmatic patients were included (75 ACO: age 61 ± 10 years, 60% women and 40 NS-IRAO: age 64 ± 9 years, 38% women). ACO patients had worse asthma control scores (1.8 ± 0.9 vs 1.4 ± 0.9, P = 0.02) and poorer asthma quality of life (5.3 ± 1.0 vs 5.9 ± 1.0, P = 0.003). In addition, ACO had higher residual volume (145 ± 45 vs 121 ± 29% predicted, P = 0.008) and a lower carbon monoxide diffusing capacity corrected for alveolar volume (90 ± 22 vs 108 ± 20% predicted, P = 0.0008). No significant differences were observed in systemic or lower airway inflammation. In conclusion, in smokers and non-smokers, the presence of IRAO in asthmatics is associated with different phenotypes that reflect the addition of smoking-induced changes to asthma physiopathology. [ABSTRACT FROM AUTHOR]

Background: A “frequent exacerbator phenotype” has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma.Aim: To compare the characteristics of frequent and nonfrequent exacerbators in asthma of different severities and to assess the stability of the exacerbator status.Methods: This was an observational study comparing baseline data from frequent (≥2 exacerbations in the past year) and nonfrequent (<2 exacerbations in the past year) exacerbators. Patients were also followed up for one year. Information regarding clinical, physiologic, and inflammatory characteristics was collected at baseline and one-year follow-up.Results: Forty-seven frequent and 53 nonfrequent exacerbators were recruited. No specific clinical, physiologic, or inflammatory characteristic was observed in the frequent as compared to the nonfrequent exacerbators at baseline. Fifty-eight percent of patients reporting frequent exacerbations at baseline remained in this group after one year of follow-up. Forty-two and 62% of patients with, respectively, mild-to-moderate asthma and severe asthma had frequent exacerbations. In apost hocanalysis according to asthma severity, frequent exacerbators with severe asthma had a higher body mass index and poorer asthma control, although they reported higher adherence to medication, in comparison to frequent exacerbators with mild-to-moderate asthma. No specific characteristics could discriminate between frequent and nonfrequent exacerbators of the same asthma severity.Conclusions: Frequent exacerbators with severe asthma present some specific characteristics not observed in frequent exacerbators with mild-to-moderate disease. However, the latter group should be identified to reassess treatment needs and potential contributing factors. [ABSTRACT FROM PUBLISHER]

Objective: To compare the prevalence of discrepancies between clinical, physiological, and inflammatory asthma control parameters between patients with asthma and obesity and patients with asthma but not obesity using the Asthma Control Scoring System (ACSS).Methods: A retrospective analysis of demographic data and ACSS scores was performed in two groups of patients with asthma (74 with obesity and 74 without obesity) paired for sex, age, and asthma severity. Scores from each asthma control parameter-clinical (respiratory symptoms), physiological (forced expiratory volume in 1 s), and inflammatory (sputum eosinophil percentage)-were compared. Discrepancy was defined as a >20% difference between two scores.Results: The prevalence of discrepancies between scores was similar between asthma patients with or without obesity. A sub-analysis on patients with uncontrolled asthma (ACSS global score <80%) showed a higher prevalence of discrepancies between the clinical and physiological scores in subjects with obesity, the clinical score being higher than the physiological one in most (87%) cases.Conclusions: Subjects with obesity and uncontrolled asthma show higher clinical scores than physiological scores, suggesting an under-evaluation of asthma symptoms. Future studies are needed to evaluate the influence of obesity on each type of asthma symptom. [ABSTRACT FROM AUTHOR]

Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2andNAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+,n = 95) and asymptomatic exposed workers (AW,n = 142). Genotyping was performed on genomic DNA, using a 5′ nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, thePTGS1rs5788 andTGFB1rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74, respectively) while theTNFαrs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, thePTGS2rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75). These results suggest that genetic variations inTNFα, TGFB1, PTGS1andPTGS2genes contribute to DA susceptibility. [ABSTRACT FROM PUBLISHER]

An editorial is presented on corticosteroids transforming the life of patients suffering from asthma. Topics include oral corticosteroids (OCS) associated with well-recognized long-term side effects and increase in mortality; and antiinflammatory agents targeting T-helper cell type 2 (Th2) inflammation with minimal side effects and with corticosteroid-sparing properties.

Background: Phosphodiesterase 4 (PDE4) inhibitors increase intracellular cyclic adenosine monophosphate (cAMP), leading to regulation of inflammatory cell functions. Roflumilast is a potent and targeted PDE4 inhibitor. The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge. Methods: 25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15. Results: Roflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen. Conclusions: This study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR. Trial Registration: ClinicalTrials.gov: NCT01365533 [ABSTRACT FROM AUTHOR]

Background: Airway hyperresponsiveness is highly prevalent in competitive swimmers, but it is unknown whether this is transient or persistent. Objectives: To document changes in airway responsiveness and airway inflammation in elite swimmers during intense training and rest. Methods: Nineteen swimmers and 16 healthy controls completed a standardized questionnaire, allergy skin prick tests, exhaled nitric oxide measurement, eucapnic voluntary hyperpnea testing, methacholine challenge, and induced sputum analysis. Testing was performed during intense swimming and after at least 2 weeks of rest. Results: Sixteen swimmers and 13 controls were atopic. Airway responsiveness to methacholine and eucapnic voluntary hyperpnea was significantly higher in swimmers than in controls (P < .0001). A significant decrease in airway responsiveness was observed from training to rest in swimmers only (P < .005). This occurred with both methacholine challenge—with PC20 values of 6.0 mg/mL and 12.8 mg/mL, respectively—and eucapnic voluntary hyperpnea testing—with a maximum fall in FEV1 after voluntary testing of 14.1 L and 10.1 L, respectively. Eight of 12 swimmers with airway hyperresponsiveness during intense training had normal airway responsiveness during rest. No airway inflammation occurred, and no significant change in this parameter was observed from training to rest. Conclusion: Training may contribute to the development of airway hyperresponsiveness in elite swimmers, but this seems reversible in many athletes after training cessation for at least 2 weeks. [ABSTRACT FROM AUTHOR]

Purpose: To compare the influence of underlying airway inflammation and lung hyperinflation on dyspnea during induced bronchoconstriction in subjects with mild asthma (or asymptomatic airway hyperresponsiveness (AAHR). Methods: Fourteen mild asthmatic and 14 AAHR subjects had methacholine and 5′-adenosine monophosphate (AMP) challenges, and induced sputum analysis. Changes in inspiratory capacity (IC) and respiratory symptom scores were measured after challenges. Perception of respiratory symptoms was recorded on a modified Borg scale. Results: The mean baseline FEV1, IC, mean provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20), the mean PC20 AMP and median inflammatory cell counts were similar in both groups. After methacholine, mean (±SD) reductions in FEV1 were 24.7±10.3% in mild asthma and 35.6±19.1% in AAHR (P>0.05); reductions in IC were, respectively, 10±12% and 24±20% (P>0.05); mean breathlessness scores at PC20 were 1.1 in mild asthma and 0 in AAHR P=0.003), and mean chest tightness scores were 1.2 in mild asthma and 0.8 in AAHR (P>0.05). Maximum chest tightness scores following MC correlated with the maximum decrease in IC in mild asthma (rs=0.75,P=0.009) and with the maximum decrease in FEV1 in AAHR (rs=0.60,P=0.04). After AMP, symptom scores were not significantly correlated with decreases in FEV1 or IC. The number of inflammatory cells was not correlated with decreases in IC after methacholine, AMP or with their PC20s, although inflammation was minimal in both groups. Conclusion: Lower breathlessness scores in AAHR compared to mild asthma were not explained by differences in lung hyperinflation nor in airway inflammation. [ABSTRACT FROM AUTHOR]

The article presents information on smoking, which can also cause asthma and its response to treatment by influencing the underlying airway inflammatory process. Variable airway obstruction and hyperresponsiveness attributed to an underlying inflammatory process and bronchial structural changes characterize asthma, a common chronic inflammatory condition. It is seen that in asthma patients, smoking is highly prevalent. In fact, many asthmatic smokers do not want to believe they are at any personal risk from smoking. Nonasthmatic smokers frequently show signs of small-airways dysfunction, airway hyperresponsiveness, and a reduction of bronchodilator response.

Background: Atopy may be a risk factor in the development of asthma. Indoor allergens are considered to be more potent asthma inducers than outdoor ones such as pollens. Lower airway inflammation may be present in non-asthmatic subjects during natural exposure to relevant allergens and may eventually lead to the development of asthma. Aims: To document seasonal variation in lower airway responsiveness and inflammation in sensitized non-asthmatic subjects, during natural exposure to allergens, and to determine whether it is more marked in those exposed to animals to which they are sensitized. Methods: Twenty-two atopic subjects were seen during and out of the pollen season. All (but the controls) were sensitized to domestic animals, and to trees, grasses or ragweed. Eleven were not exposed to animals at home and 8 were exposed. They were compared with 3 normal controls. A respiratory questionnaire was administered, allergy skin prick tests, spirometry, methacholine challenge, blood and induced sputum with differential cell counts were obtained during the pollen season for all subjects. These tests were repeated out of the pollen season. Results: Throughout the study, none of the subjects had asthma symptoms. Mean PC[sub 20] was significantly lower in subjects exposed to animals compared with unexposed subjects or controls, both during and out of the pollen season. In season, subjects exposed to animals had significantly higher sputum eosinophil numbers than unexposed or normal control subjects. Conclusions: Non-asthmatic atopic subjects show variable degrees of airway responsiveness and inflammation. However, subjects exposed to animals show higher airway eosinophilia, which may suggest they are at increased risk of developing airway hyperresponsiveness and asthma.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Sleep apnea hypopnea syndrome (SAHS) is a predictive factor of cardiovascular disease. We hypothesized that SAHS could influence coronary atherosclerosis plaque volume as assessed by 3-dimensional intravascular ultrasound (3D-IVUS). Methods: Participating patients were identified from 2 studies assessing the progression of atherosclerosis in stable coronary artery disease using coronary 3D-IVUS. Results: Nineteen patients, aged 61±8 years, with a body mass index of 29±5 kg/m2 were studied. Increased apnea–hypopnea index (AHI) ≥15 was found in 12/19 patients (63%). Patients with AHI≥15 had larger coronary atherosclerotic plaque volume than patients with AHI<15 (238±69 mm3 vs 169±64 mm3, p =0.047) and the difference was even larger in patients with obstructive apnea/hypopnea episodes compared to patients without (243±70 mm3 vs 170±59 mm3, p =0.03). There was a significant positive correlation between obstructive AHI and coronary atherosclerotic plaque volume (r =0.6, p =0.01). A significant positive correlation was also demonstrated between respiratory arousal index and coronary atherosclerotic plaque volume (r =0.6, p =0.02) and between total arousal index and coronary atherosclerotic plaque volume (r =0.5, p =0.03). Conclusion: In patients with stable coronary artery disease, there was a significant relationship between the frequency of obstructive sleep apnea/hypopnea episodes and sleep fragmentation and the importance of coronary atherosclerotic plaque volume. 3D-IVUS is well suited to correlate coronary atherosclerosis and sleep breathing disorders at early stages. [Copyright &y& Elsevier]

The endocannabinoid (eCB) 2‐arachidonoyl‐gycerol (2‐AG) modulates immune responses by activating cannabinoid receptors or through its multiple metabolites, notably eicosanoids. Thus, 2‐AG hydrolysis inhibition might represent an interesting anti‐inflammatory strategy that would simultaneously increase the levels of 2‐AG and decrease those of eicosanoids. Accordingly, 2‐AG hydrolysis inhibition increased 2‐AG half‐life in neutrophils. Under such setting, neutrophils, eosinophils, and monocytes synthesized large amounts of 2‐AG and other monoacylglycerols (MAGs) in response to arachidonic acid (AA) and other unsaturated fatty acids (UFAs). Arachidonic acid and UFAs were ~1000‐fold more potent than G protein‐coupled receptor (GPCR) agonists. Triascin C and thimerosal, which, respectively, inhibit fatty acyl‐CoA synthases and acyl‐CoA transferases, prevented the UFA‐induced MAG biosynthesis, implying glycerolipid remodeling. 2‐AG and other MAG biosynthesis was preceded by that of the corresponding lysophosphatidic acid (LPA). However, we could not directly implicate LPA dephosphorylation in MAG biosynthesis. While GPCR agonists poorly induced 2‐AG biosynthesis, they inhibited that induced by AA by 25%‐50%, suggesting that 2‐AG biosynthesis is decreased when leukocytes are surrounded by a pro‐inflammatory entourage. Our data strongly indicate that human leukocytes use AA and UFAs to biosynthesize biologically significant concentrations of 2‐AG and other MAGs and that hijacking the immune system with 2‐AG hydrolysis inhibitors might diminish inflammation in humans. [ABSTRACT FROM AUTHOR]

Background We have previously demonstrated that persistent symptoms following functional endoscopic sinus surgery for chronic rhinosinusitis (CRS) is associated with Gram-negative bacterial carriage. Mechanisms for this remain unknown. We wished to determine whether Gram-negative carriage in patients with CRS with nasal polyposis is associated with a more severe inflammatory phenomenon. Methods Three hundred and thirty-seven patients with CRS with nasal polyposis (CRSwNP) previously phenotyped for genetic association studies with questionnaire, serum biomarkers, and endoscopically-obtained swab cultures were studied. These were separated according to the presence (wGN) or absence (sGN) of Gram-negative bacterial carriage; demographic parameters and available serum biomarkers (complete blood count [CBC], total immunoglobulin E [IgE]) were then compared. Subgroup analysis for Pseudomonas aeruginosa (GNwPa) and non- Pseudomonas Gram-negative bacteria (GNsPs) was performed in order to explore potentially differential roles of these bacteria. Results Gram-negative bacterial carriage was not associated with a difference in demographic parameters or serum biomarkers. However, P. aeruginosa carriage was associated with a higher self-reported incidence of asthma (GNwPa 79%, sGN 57%; p = 0.048). Interestingly, serum IgE was increased in the non- Pseudomonas Gram-negative population (GNsPs: 338 IU/mL, sGN: 195 IU/mL; p = 0.026). Conclusion CRSwNP patients colonized with Gram-negative bacteria have a similar pattern of inflammation as assessed by serum biomarkers to those colonized with Gram-positive ones. Gram-negative bacteria may contribute to development of a T helper 2 (Th2) phenotype via other mechanisms, possibly via Toll-like receptor 4 (TLR4)-mediated interleukin 33 (IL-33) production. Differences in phenotype associated with Pseudomonas species carriage suggest a different behavior than other Gram-negative bacteria, supporting their importance as disease modifiers in CRSwNP. [ABSTRACT FROM AUTHOR]

Background Smoking negatively affects postoperative evolution in patients with chronic rhinosinusitis (CRS); however, the mechanism remains incompletely described. In the lung, smoking increases expression of proinflammatory genes and is associated with an elevation of inflammatory serum markers. Our objective is to determine the impact of smoking on these biomarkers in CRS. Methods Two existing populations of patients previously phenotyped for genetic association studies (206 patients with refractory CRS and 408 patients with CRS and nasal polyposis) were stratified according to self-reported smoking status and available serum biomarkers (complete blood count [CBC], total immunoglobulin E [IgE]). Asthma and bacterial cultures were evaluated. Results Active smoking was low in both groups (genetics of chronic rhinosinusitis 1 [GCRS1]: 11.2%; genetics of chronic rhinosinusitis 2 [GCRS2]: 9.4%). Total white blood cell (WBC) count was significantly higher in active smokers than in those who had never smoked and ex-smokers. Serum eosinophilia and prevalence of self-reported asthma was lower in active smokers than never-smokers. In the GCRS2 population, endoscopically-collected cultures trended toward a lower recovery rate of Staphylococcus aureus in smokers ( p = 0.07). Never-smokers and ex-smokers had similar levels of WBCs and eosinophils. Conclusion Our study reveals that active tobacco smoking is associated with increases in markers of systemic inflammation in patients with CRS. The proinflammatory effect of smoking seems not only to act locally on sinus mucosa as previously described, but may also influence levels of inflammatory biomarkers systemically, suggesting that smoking-induced changes have profound implications for health. Nevertheless, these changes may be potentially reversible; thus smoking cessation in CRS patients is strongly advised, and may have an impact on response of CRS to therapy. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus ( S. aureus) has been implicated in the pathogenesis of chronic rhinosinusitis (CRS). However, host factors contributing to susceptibility to S. aureus colonization in CRS remain unknown. We wish to investigate, using a pooled genomewide association study (pGWAS), single-nucleotide polymorphisms (SNPs) associated with S. aureus carriage in CRS patients. Methods An existing population of 408 CRS patients and 190 controls was prospectively recruited for genetic association studies. All CRS patients had an endoscopic swab culture as part of phenotyping. A pGWAS compared DNA pools from patients with and without S. aureus colonization using the Illumina HumanHap 1M BeadChip, which interrogates 1 million SNPs. Top-ranked SNPs associated with S. aureus colonization were selected according to biallelic differences and silhouette rank, and confirmed by individual genotyping using the Sequenom platform. PLINK software was used for genetic association tests. Ingenuity pathway analysis was used to identify canonical and signaling pathways enriched for genes neighboring associated SNPs, as well as identification of the underlying biological mechanisms. Results Thirty-nine top priority SNPs were selected for individual genotyping. Out of 39 SNPs, 23 were associated ( p < 0.05) with S. aureus colonization in CRS patients. These SNPs are located within or near 21 genes reported to be implicated in several diseases, endocytic internalization, and bacterial recognition. Conclusion These results suggest novel host genetic factors influencing susceptibility to S. aureus colonization in CRS. Identifying implicated mechanisms may offer new insights into pathogenesis of CRS. [ABSTRACT FROM AUTHOR]

Purpose: Obesity is associated with left ventricular diastolic dysfunction and altered heart rate variability, as well as pulmonary dysfunction. The relationship between asthma and cardiac dysfunction in severely obese subjects is unknown, although it has been hypothesized that cardiac dysfunction may contribute to increase airway hyper-responsiveness (AHR). This study aimed to determine if AHR is associated with left ventricular diastolic dysfunction and heart rate variability in severely obese subjects. Methods: Sixty-one subjects with severe obesity (BMI ≥35 kg/m² with comorbidities) completed this study. All subjects completed respiratory questionnaires, spirometry, lung volume measurements, methacholine inhalation test, 24hour Holter monitoring and a complete echocardiography evaluation. Blood samples were obtained for measurement of metabolic markers. Subjects with AHR, defined by a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) <8 mg/ml, were compared with those with no AHR (PC20 ≥8 mg/ml). Results: According to these criteria, 32 subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml respectively, p<0.001). The groups were similar for anthropometric data and comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo-B, C-reactive protein (CRP) and pro-BNP levels were also comparable between groups (p>0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices of heart rate variability and overall cardiac function were similar in subjects with or without AHR but grade 2 left ventricular diastolic dysfunction was more prevalent in subjects with AHR (p=0.037). Conclusions: Altered cardiac function, dysglycemia and dyslipidemia do not seem to be significantly associated with AHR in severely obese subjects in contrast to systemic inflammation. [ABSTRACT FROM AUTHOR]