Small Airways Of Patients Research Articles

Small Airway Disease in Patients with Chronic Obstructive Pulmonary Disease.

Small airway disease (SAD) has been recognized for many years as a central feature of chronic obstructive pulmonary disease (COPD). Histopathology studies have shown that the narrowing and destruction of small airways in COPD combined with inflammatory cell infiltration in the submucosa increases the severity of the disease. SAD is present in the early stages of COPD and becomes more widespread over time as the disease progresses to more severe COPD. The development of inhalers containing extra-fine particles allows the small airways to be pharmacologically targeted. Recent clinical trials have shown the efficacy of extra-fine triple therapy that targets the small airways in patients with COPD. This article reviews the importance and treatment of SAD in COPD.

Small airways in asthma

Asthma is a chronic inflammatory lung disease characterized by reversible obstruction of airways and bronchial hyperresponsiveness. In recent years there has been a growing interest in the role of the small airways in asthma and there is increasing evidence that they contribute significantly to the clinical expression of asthma. Numerous studies have shown that inflammation is present in the small airways of patients with asthma and that it may be more intense than that found in the large airways, particularly in severe asthma, nocturnal asthma, coexisting asthma and obesity and asthma in smokers. Currently there is no accepted single lung function parameter to detect small airways dysfunction. Recent data show that impulse oscillometry is a promising diagnostic tool to assess the involvement of the small airways. The use of corticosteroids in extrafine formulation, whether alone or in fixed combinations with long-acting b2 agonists, improves drug distribution throughout the bronchial tree, enhancing the therapeutic effect with lower doses of drugs.

Cigarette smoke affects dendritic cell maturation in the small airways of patients with chronic obstructive pulmonary disease.

The aim of the present study was to characterize and quantify the numbers and expression levels of cells markers associated with dendritic cell (DC) maturation in small airways in current smokers and non-smokers with or without chronic obstructive pulmonary disease (COPD). Lung tissues from the following 32 patients were obtained during resection for lung cancer: Eight smokers with COPD, eight non-smokers with COPD, eight current smokers without COPD and eight non-smokers without COPD, serving as a control. The tissue sections were immunostained for cluster of differentiation (CD)83+ and CD1a+ to delineate mature and immature DCs, and chemokine receptor type 7 (CCR7+) to detect DC migratory ability. Myeloid DCs were collected from the lung tissues, and subsequently the CD83+ and CCR7+ expression levels in the lung myeloid DCs were detected using flow cytometry. The expression levels of CD83+, CD1a+ and CCR7+ mRNA in total lung RNA were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Evident chronic bronchitis and emphysema pathological changes were observed in the lung tissues of patients with COPD. The results revealed that the numbers of CD83+ and CCR7+ DCs were reduced but the numbers of CD1a+ DCs were significantly increased in the COPD group as compared with the control group (P<0.05, respectively). Using RT-qPCR, the expression levels of CCR7+ and CD83+ mRNA were found to be reduced in the smokers with COPD as compared with the non-smokers without COPD group (P<0.05, respectively). Excessive local adaptive immune responses are key elements in the pathogenesis of COPD. Cigarette smoke may stimulate immune responses by impairing the homing of airway DCs to the lymph nodes and reduce the migratory potential of DCs. The present study revealed that COPD is associated with reduced numbers of mature CD83+ DCs and lower CCR7+ expression levels in small airways.

DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.

DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate whether changes in gene expression are associated with these disruptions. Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2-related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD.

Epithelial to mesenchymal transition is increased in patients with COPD and induced by cigarette smoke

BackgroundCigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of remodelling, peribronchiolar fibrosis is observed in the small airways of patients with COPD and contributes...

Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue.

IntroductionAirway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients.MethodsWe retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t-test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test.ResultsThirty-one ARDS patients (A: PaO2/FiO2 ≤200, 45 ± 14 years, 16 males) and 11 controls (C: 52 ± 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 ± 27.2%, C:76.7 ± 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 ± 35.2%, C:21.8 ± 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 ± 54.3 μm, C:86.4 ± 33.3 μm, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P ≤0.03). The extension of normal epithelium showed a positive correlation with PaO2/FiO2 (r2 = 0.34; P = 0.02) and a negative correlation with plateau pressure (r2 = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r2 = 0.27; P = 0.04).ConclusionsStructural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

BackgroundDendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.MethodsMyeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.ResultsTwo segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.ConclusionsMyeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.

Anatomy, pathology, and physiology of the tracheobronchial tree: Emphasis on the distal airways

This article covers the airway tree with respect to anatomy, pathology, and physiology. The anatomic portion discusses various primate groups so as to help investigators understand similarities and differences between animal models. An emphasis is on distal airway findings. The pathology section focuses on the inflammatory responses that occur in proximal and distal airways. The physiologic review brings together the anatomic and pathologic components to the functional state and proposes ways to evaluate the small airways in patients with asthma.

Decreased Small Airway and Alveolar CD83+ Dendritic Cells in COPD

Dendritic cells (DCs) have been reported to be increased in the small airways of patients with COPD, but the maturity status of these cells is unclear. We have quantified the numbers of cells expressing markers associated with DC maturation. Lung tissue was obtained at resection for lung cancer from 41 patients with COPD (30 current smokers and 11 ex-smokers; 32 steroid-treated patients and 9 steroid-naïve patients), 19 ex-smokers without COPD and 9 never-smokers without COPD. Tissue sections were immunostained for CD1a to mark immature DCs, and for CD83, fascin, and DC-lysosome-associated membrane protein (DC-LAMP) to delineate mature DCs. The volume density (ie, the volume of DCs as the percentage volume of the airway wall) comprising CD83+ DCs was significantly reduced in patients with COPD (median, 0; range, 0 to 5.1%) vs smokers (median, 2.8%; range, 0 to 10.2%) and never-smokers (median, 1.9%; range, 0.8 to 5.1%) without COPD (p = 0.000 and 0.012, respectively). Using a semiquantitative score for the alveolar wall, CD83+ DCs also were decreased in patients with COPD (median, 0; range, 0 to 2%) vs smokers (median, 1%; range, 0 to 2%) and never-smokers (median, 1%; range, 0.7 to 2%) without COPD (p = 0.004 and 0.04, respectively). No differences were detected in CD83+ DCs between current smokers and ex-smokers with COPD or between steroid-treated and steroid-naive patients. No differences were detected in CD1a+ DCs. Fascin and DC-LAMP were found to have poor specificity for mature DCs. COPD is associated with decreased numbers of (mature) CD83+ DCs in small airways and alveoli. The relevance of such a reduction on pulmonary immune responses requires further investigation.

Small airways disease in asthma

A mounting body of physiologic and pathologic evidence indicates that asthma involves the central and the more distal airways. In patients with asthma, the peripheral lung accounts for a significant portion of airway resistance and, similar to the large airways, the small airways have been shown to be hyperresponsive to nonspecific stimuli, such as methacholine. Cellular inflammation, consisting of an infiltrate rich with lymphocytes and eosinophils, is present in the small airways of patients with asthma and may be more intense than that observed in the large airways. Clinical assessment of the peripheral airways continues to be a challenge, and new techniques, such as quantitative analysis of chest CT images, have proven to be useful research tools. The recognition of small airways involvement in asthma has clinical relevance, as new formulations of inhaled corticosteroids with smaller particle aerosols may be more effective in addressing this component of asthma.

Effect of Inhalated Bronchodilators on Air Trapping in Patients with Stable Asthma

Air trapping is frequently observed during high-resolution computed tomography (HRCT) of patients with asthma, but whether the condition is reversible has not been thoroughly investigated. The aim of the present study was to evaluate reversibility of air trapping in response to bronchodilator. Ten never-smokers with stable asthma enrolled in the study. Spirometry and HRCT were performed before and after bronchodilator inhalation. Air trapping remained unchanged, although significant reversibility of FEV1 was observed. Air trapping scores correlated significantly with airway wall thickness. These observations suggest that air trapping is irreversible and that it represents structural remodeling of small airways in patients with stable asthma.

The role of airway smooth muscle in the pathogenesis of airway wall remodeling in chronic obstructive pulmonary disease.

Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to beta-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in beta-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting beta-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.

Airway proteoglycans are differentially altered in fatal asthma

It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter < or =6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (microm2)/epithelial basement membrane length (microm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 microm, C = 3.97 +/- 1.17 microm, p = 0.042; lumican: A = 1.97 +/- 0.37 microm, C = 5.66 +/- 0.99 microm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 +/- 0.84 microm, C = 5.16 +/- 0.61 microm, p = 0.045; large: A = 18.38 +/- 1.94 microm, C = 11.90 +/- 2.86 microm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma.

Oligoclonal CD4+T Cells in the Lungs of Patients with Severe Emphysema

Within the lungs of patients with severe emphysema, inflammation continues despite smoking cessation. Foci of T lymphocytes in the small airways of patients with emphysema have been associated with disease severity. Whether these T cells play an important role in this continued inflammatory response is unknown. The aim of this study was to determine if T cells recruited to the lungs of subjects with severe emphysema contain oligoclonal T-cell populations, suggesting their accumulation in response to antigenic stimuli. Lung T-cell receptor (TCR) Vbeta repertoire from eight patients with severe emphysema and six control subjects was evaluated at the time of tissue procurement (ex vivo) and after 2 weeks of culture with interleukin 2 (in vitro). Junctional region nucleotide sequencing of expanded TCR-Vbeta subsets was performed. No significantly expanded TCR-Vbeta subsets were identified in ex vivo samples. However, T cells grew from all emphysema (n = 8) but from only one of the control lung samples (n = 6) when exposed to interleukin 2 (p = 0.0013). Within the cultured cells, seven major CD4-expressing TCR-Vbeta subset expansions were identified from five of the patients with emphysema. These expansions were composed of oligoclonal populations of T cells that had already been expanded in vivo. Severe emphysema is associated with inflammation involving T lymphocytes that are composed of oligoclonal CD4+ T cells. These T cells are accumulating in the lung secondary to conventional antigenic stimulation and are likely involved in the persistent pulmonary inflammation characteristic of severe emphysema.

Quantitative Analysis of Bronchial Wall Vascularity in the Medium and Small Airways of Patients With Asthma and COPD

Submucosal hypervascularity is part of airway remodeling in patients with asthma; however, its existence in the small airways and its contribution to airflow limitation remain controversial. We investigated bronchial wall vascularity and angiogenic cells between medium airways (inner diameter, 2 to 5 mm) and small airways (inner diameter, < 2 mm) in patients with asthma (n = 9) and COPD (n = 11), and in 8 control subjects. The lung specimens obtained during surgery were immunostained to detect CD31, CD34, vascular endothelial growth factor, and basic fibroblast growth factor. The number of vessels in both the medium and small airways in patients with asthma was significantly (p < 0.01) increased compared to those in patients with COPD and control subjects, and the percentage of vascularity was significantly (p < 0.01) increased in the medium airways in asthma patients and in the small airways in COPD patients. Patients with moderate asthma showed a greater increase in vascularity than those with mild asthma (p < 0.01), and the number of angiogenic factor-positive cells increased in asthma patients compared with control subjects. In asthmatic subjects, inverse correlations were found between FEV(1) percentage of predicted and the number of vessels (r = -0.85; p < 0.01), or the percentage of vascularity (r = -0.72; p < 0.03) in the inner area of the medium airways, but they were not found for the small airways. In COPD patients, no correlations were demonstrated. The number of vessels in the medium and small airways in asthma patients shows a greater increase than those in COPD patients, and the vascular area in the small airways is increased in COPD patients but not in asthma patients. Enhanced vascularity in the inner area of the medium airways, but not in the small airways, might contribute to airflow limitation in asthma patients.

Long-term clearance from small airways in patients with cystic fibrosis

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

Hydrofluoroalkane-134A Beclomethasone or Chlorofluorocarbon Fluticasone: Effect on Small Airways in Poorly Controlled Asthma

Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, ≥ 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 µg each morning and 110 µg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25–75% of the vital capacity (FEF25–75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25–75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

Differences in airway remodeling between asthma and chronic obstructive pulmonary disease.

The functional consequence of asthma and chronic obstructive pulmonary disease (COPD)is airflow limitation, which is mostly reversible in asthma and not fully reversible in COPD. In both diseases, inflammatory conditions are associated with cellular and structural changes,referred to as remodeling, and these structural changes may lead to thickening of the airway wall, thereby promoting airway narrowing and airflow limitation. However, the pattern of infiltrated cells and the pattern of structural changes occur differently in the two diseases. In asthma, CD4+, T lymphocytes, eosinophils, and mast cells are the predominant cells involved,whereas in COPD, CD8+, T lymphocytes, and macrophages are predominantly involved. In severe cases of asthma and COPD, neutrophil infiltration becomes evident. Regarding structural changes, epithelial injury and early thickening of reticular basement membrane are highly characteristic of the airway wall of asthmatics. Increases in airway smooth muscle mass occur in large airways of severe asthmatics and in small airways of patients with COPD. Thickening of the airway wall, goblet cell hyperplasia, mucous gland hypertrophy, and the luminal obstruction caused by inflammatory exudates and mucous are features of both asthma and COPD. Squamous epithelial metaplasia and airway wall fibrosis are commonly observed characteristics of COPD. Destruction and fibrosis of the alveolar wall occur in COPD but not in asthma. The remodeling processes accompanied by chronic inflammatory infiltrates interact in a complex fashion and contribute to the development of airflow limitation in both asthma and COPD.

Hydrofluoroalkane-134a beclomethasone or chlorofluorocarbon fluticasone: Effect on small airways in poorly controlled asthma

Inflammation in asthma extends into the small airways ( 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, � 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 mg each morning and 110 mg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly ( p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25 – 75% of the vital capacity (FEF25 – 75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly ( p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25 – 75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group ( p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

Improved Small Airway Function With Fluticasone Propionate/Salmeterol versus Ipratropium/Albuterol Therapy in Patients With Chronic Obstructive Pulmonary Disease (COPD

PURPOSE: The patency of small airways is assessed by the forced expiratory flow (FEF25–75%), which is decreased in obstructive airways due to mucus secretion, bronchospasm, inflammation, and alveolar destruction. The purpose of this analysis was to determine the effect of fluticasone propionate 250 mcg/salmeterol 50 mcg therapy (FSC 250/50) compared to ipratropium 36mcg/ albuterol 206mcg (Ipr/Alb) on the small airways in patients with COPD.