Diaphragm paralysis after nephrectomy.
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Diaphragm↗
Biomedical subjects
A Chetta
Publications and source records attributed to A Chetta.
Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma.
BACKGROUND: There is increasing in vitro evidence to support a role for vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, as a mediator of fibrosis associated with neovascularization. OBJECTIVE: We tested the hypothesis that VEGF is involved both in increased airway mucosal vascularity and in the subepithelial fibrosis of asthmatic patients. METHODS: Bronchial biopsies were performed in 24 asthmatic patients and eight healthy controls. Immunostaining, using computerized image analysis, was performed using monoclonal antibodies against VEGF(+) cells, type IV collagen, to outline the basement membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils, respectively. RESULTS: The counts of VEGF(+) cells (P<0.05), mast cells and EG2(+) cells (both P<0.01) were higher in asthmatics than in controls. The number of vessels, the vascular area in the lamina propria, and the basement membrane thickness were significantly higher in asthmatics than in healthy volunteers (P<0.01). Moreover, in asthmatic patients, the number of VEGF(+) cells was significantly related to the number of vessels (P<0.01), to mast cells (P<0.01) and to basement membrane thickness (P<0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF(+) cells (P<0.05), vessel number (P<0.05), vascular area (P<0.05) and basement membrane thickness (P<0.05) in a subgroup of asthmatic patients. CONCLUSIONS: This study shows that VEGF, in addition to being involved in the vascular component of airway remodelling, may play a role in the thickening of the basement membrane in asthma.
Administration, Inhalation↗
[Educational programs and self-management in bronchial asthma].
Bronchial asthma is one of the most common chronic diseases in the world and can affect people of all ages. In the last few years there has been a considerable improvement in the etiopathogenetic knowledge of the disease and extremely effective anti-asthmatic drugs are available. However, asthma-related morbidity and mortality are increased, especially in Western countries. In an attempt to reverse this negative trend, for a number of years national and international guidelines on asthma have been published all over the world. These guidelines have the aim of improving asthma diagnosis and treatment and of conveying a fundamental educational message both to health workers and to patients and their families. From the data in the literature it can be clearly seen that only through the application of valid educational programs is it possible for asthmatics to improve their knowledge of the disease and to understand how they can look after themselves by a careful evaluation of their own symptoms and respiratory function. They should also be aware of the drugs available for the treatment of both acute asthmatic crises and chronic asthma, but especially of the fact that this chronic inflammatory affection can be fully treated. In particular, an educational program organized with groups of maximum 10-12 people attending 2 lessons and with helpful training tools, can increase significantly asthma knowledge, treatment compliance and patient self-management. The aim of this review is to highlight the importance of educational programs and those obscure areas which slow down their large scale application and universal acceptance.
Adult↗
Eosinophils in induced sputum from asymptomatic smokers with normal lung function.
Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD). However, only 10-15% of smokers develop the disease and early changes within the airways are poorly defined. We aimed to compare cell profiles in induced sputum (IS) from asymptomatic smokers to that from healthy subjects, and to ascertain whether or not inflammatory cells in IS are related to lung function and smoking habit. We recruited 34 heavy, non-allergic asymptomatic smokers with normal lung function and 15 healthy volunteers, who performed lung function tests and IS by hypertonic saline (3%) solution. In smokers, significantcorrelation between pack-years and FEF25-75 (rs = -0.43, P < 0.02) was found. In IS, smokers had higher counts of macrophages (P < 0.01) and eosinophils (P < 0.02), when compared to those of healthy subjects. Additionally, eosinophils were found in IS of 14 out of 34 smokers, with eosinophils had a higher pack-years (31 +/- 25 vs. 13 +/- 10, P = 0.02) and lower FEF 25-75% value (78% +/- 34 vs. 100% +/- 23. P < 0.04). when compared to smokers without eosinophils. Additionally, on the basis of regression equations by stepwise multiple regression analysis, eosinophils were predicted by pack-years (r2 = 0.41). Our results showed that asymptomatic smokers have evidence of inflammatory cells in IS samples. In addition, we found thatthe degree of eosinophilic inflammation is related to early changes of lung function and can be predicted by smoking habit.
Adult↗
Six-minute walking test in cystic fibrosis adults with mild to moderate lung disease: comparison to healthy subjects.
The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities.
Adolescent↗
Whistle mouth pressure as test of expiratory muscle strength.
Expiratory muscle strength is a determinant of cough function. Mouth pressures during a maximal static expiratory effort (PE,max) are dependent on patient motivation and technique and low values are therefore difficult to interpret. This study hypothesized that a short, sharp and maximal expiration through a narrow aperture, a "whistle", might provide a complementary test of expiratory muscle strength. To obtain a maximal whistle, subjects (27 healthy volunteers and 10 patients with amyotrophic lateral sclerosis) were asked to perform a short, sharp blow as hard as possible, from total lung capacity, through a reversed paediatric inhaler whistle, connected to a flange-type mouthpiece. In both healthy subjects and patients, whistle mouth pressure (Pmo,W) was closely related to the pressure measured in the oesophagus and stomach during the same manoeuvre. In healthy subjects, Pmo,W and PE,max correlated with wide limits of agreement, although Pmo,W values were significantly higher than PE,max (131+/-31 cmH2O versus 101+/-27 cmH2O, p<0.0001). In patients, it was also found that Pmo,w and PE,max values were strongly related (r=0.937, p<0.0001). In healthy subjects, the intraclass correlation coefficient and the variation coefficient for Pmo,W repeated measurements were respectively 0.88 and 7.0%. However Pmo,W and PE,max were always smaller than the gastric pressure generated by a maximal cough. It is concluded that mouth whistle pressure, a noninvasive, reproducible and simple test, provides a reliable measure of expiratory muscle strength in healthy subjects that is acceptable to patients and can be used in a complementary fashion to maximal static expiratory effort.
Adult↗
Relationship between outcome measures of six-minute walk test and baseline lung function in patients with interstitial lung disease.
BACKGROUND AND AIM OF THE WORK: In patients with interstitial lung disease (ILD), the six-minute walk test (6MWT) has been rarely used, and up till now, the relationship between outcome measures of the test and baseline lung function has not yet been examined. Therefore, we assessed walk distance, oxygen desaturation, and breathlessness perception during 6MWT, and their relationships to baseline lung function in patients with ILD. METHODS: Forty ILD patients with history of breathlessness during physical exertion performed a 6MWT following a standard protocol. Breathlessness perception during walk was assessed by visual analogue scale (VAS, in mm). RESULTS: The mean walk distance was 487 meters (range 271-689). Mean baseline oxygen saturation (Base SpO2, %) was 94% and was reduced during walk, either as mean oxygen saturation (Mean SpO2, 89%, p < 0.001) or as mean fall in oxygen saturation during walk (Fall SpO2, 5%). Furthermore, VAS significantly increased after walk (5 mm to 44 mm, p < 0.001). A close relationship of TLco and TLC to walk distance and Fall SpO2 was found (r = 0.45 and 0.42 and r = -0.75 and -0.64, respectively; p < 0.001, each). On the basis of regression equations by stepwise multiple regression analysis, walk distance was predicted by age and FVC (r2 = 0.50), Mean SpO2 by TLco and Base SpO2 (r2 = 0.80), and Fall SpO2 only by TLco (r2 = 0.57). Breathlessness perception was not reliably predicted by any assessed variables. CONCLUSIONS: We confirmed that 6MWT provides a global evaluation of sub-maximal exercise capacity in ILD patients. We also found that walk distance and oxygen desaturation, but not breathlessness perception during walk, are strictly related to baseline lung function.
Adult↗
Eosinophil apoptosis in induced sputum from patients with seasonal allergic rhinitis and with asymptomatic and symptomatic asthma.
BACKGROUND: Eosinophilic inflammation is known to play an important role in the pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is characterized by morphologic cell changes and leads to recognition and ingestion by macrophages. Apoptosis could be an important mechanism controlling the resolution of tissue eosinophilia. OBJECTIVE: This study was designed to investigate the presence of apoptotic eosinophils in induced sputum of patients with seasonal allergic rhinitis (SAR), when examined during natural pollen exposure and of patients with perennial asthma of different degrees of severity. METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The severity of asthma was assessed by clinical scoring. Sputum was induced following a standard method and differential cell count was estimated. Eosinophils showing cell shrinkage and nuclear coalescence were classified as apoptotic. The number of apoptotic eosinophils was expressed as the percentage of total cells in sputum and as the proportion of apoptotic eosinophils relative to normal bilobed eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in the SA group was significantly greater than that in the SAR and the AA groups (P < .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA group was significantly lower than that in the SAR group (P < .001) and in the SA group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was significantly greater than in the AA group (P < .05) and in the SA group (P < .05). There was no difference in the apoptotic ratio between the AA and SA groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are detectable in induced sputum of allergic patients. Further, the results of our study suggest that apoptosis could be an important mechanism in the control of acute eosinophilic inflammation in patients with SAR exposed to the sensitizing antigens. It appears that the apoptotic mechanism could be less effective in controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic inflammation.
Adult↗
Role of induced sputum in interstitial lung disease.
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Adult↗
Induced sputum: diagnostic value in interstitial lung disease.
Induced sputum by inhalation of hypertonic saline solution is a noninvasive technique used to collect cellular and soluble material from lung airways. During the past decade, this method has been widely used to assess airway inflammation in asthma and chronic obstructive pulmonary disease, since it produces reliable results and compares favorably to other invasive techniques, such as biopsy and bronchoalveolar lavage (BAL). Induced sputum has been recently used to study interstitial lung disease (ILD), more specifically pneumoconiosis, sarcoidosis, and nongranulomatous ILD. Moreover, results from induced sputum supplied information comparable to BAL findings for occupational lung disease and were able to distinguish sarcoidosis patients from healthy subjects and from patients with nongranulomatous ILD. Although induced sputum had previously provided promising results in assessing patients with ILD, its diagnostic role has not yet been well defined. Further studies of the evaluation by induced sputum of grading of severity, follow-up of disease, and effects of treatment are needed. Additionally, to date no specific studies have been undertaken to evaluate the safety and functional effects of sputum induction on patients with ILD. In conclusion, we think that induced sputum can be used as a complementary tool to BAL both in research and in clinical monitoring of patients with ILD.
Bronchoalveolar Lavage↗
The effect of inflammation on mucociliary clearance in asthma: an overview.
Mucociliary clearance (MCC) is one of the most important nonspecific defense mechanisms of the respiratory tract, and its impairment is a well-documented feature of chronic respiratory diseases, including asthma. In vitro and in vivo data suggest that several inflammatory mediators influence the mucociliary apparatus. Epithelial damage and functional abnormalities have been described in bronchial asthma, along with changes in mucus-secreting cells and the chemical and rheological properties of airway fluid. Although the mechanisms of MCC impairment in asthma are not clearly understood, data in the recent literature suggest that airway inflammation plays a major role. In this article, we review studies on MCC alterations in light of up-to-date findings on pathogenetic mechanisms in asthma.
Animals↗
Induced sputum in patients with newly diagnosed sarcoidosis: comparison with bronchial wash and BAL.
OBJECTIVES: Sarcoidosis is characterized by a diffuse alveolar inflammatory process, although bronchial airways are often involved. This study compares the cellular profiles of induced sputum (IS), bronchial washing (BW), and BAL in newly diagnosed sarcoidosis patients to those in control subjects, and examines whether inflammatory cell counts from IS are correlated with inflammatory cell counts from BW and BAL in sarcoidosis patients. PATIENTS AND MEASUREMENTS: We recruited 15 untreated patients with stage I and II pulmonary sarcoidosis and 12 healthy volunteers. Sputum was induced with hypertonic saline solution in all individuals. Bronchoscopy was performed on a different occasion in all patients and in five control subjects. RESULTS: Mean lymphocyte counts in IS, BW, and BAL fluid from sarcoidosis patients were significantly higher than in control subjects (9.4% vs 3.8%, p < 0.05; 12.6% vs 3.9%, p < 0.05; 24.1% vs 2.6%, p < 0.05, respectively). Moreover, total cell count and percentage of epithelial cells in IS were significantly higher in sarcoidosis patients than in control subjects (p < 0.01 and p < 0.05, respectively). In sarcoidosis patients, comparison between different samples showed significantly higher percentages of macrophages in BW and BAL than in IS (p < 0.05 and p < 0.01, respectively), whereas the percentage of neutrophils was higher in IS compared with BW and BAL (p < 0.01 and p < 0.001, respectively). Finally, the percentage of lymphocytes in IS was significantly lower than that in BAL (p < 0.05) but not that in BW. CONCLUSIONS: We demonstrated that, compared with IS in healthy control subjects, IS in untreated pulmonary sarcoidosis patients contains more total cells, lymphocytes, and epithelial cells. Although the relative proportion of inflammatory cells in the three samples differed, lymphocyte counts in IS were high. This finding suggests that IS could be used as a valuable alternative to more conventional invasive techniques in clinical assessment of pulmonary sarcoidosis patients.
Administration, Inhalation↗
Effect of sputum induction on spirometric measurements and arterial oxygen saturation in asthmatic patients, smokers, and healthy subjects.
BACKGROUND: Sputum production induced by inhalation of hypertonic saline solution has been proposed as a technique to collect secretions and inflammatory cells from the airways of subjects with bronchial asthma or with a history of smoking. The aim of this study was to determine the effect of a sputum induction procedure on spirometric results and arterial oxygen saturation (SaO(2)) in asthmatic patients, smokers, and healthy subjects. METHODS: We recruited 14 subjects suffering from asthma (11 men and 3 women; age range, 18 to 49 years), 14 subjects with a history of smoking (5 men and 9 women; age range, 23 to 64 years), and 9 healthy volunteers (7 men and 2 women; age range, 28 to 54 years). To obtain a sample of induced sputum, all subjects inhaled a mist of 3% hypertonic saline solution nebulized for 5 min and repeated the cycle no more than four times. Asthmatic patients were pretreated with 200 microg salbutamol (inhaled). During sputum induction, the transcutaneous SaO(2) was continuously measured and baseline, fall, and the differences between baseline and fall SaO(2) were recorded. Additionally, we measured the duration of mild desaturation (change in SaO(2), < 4%) and of marked desaturation (change in SaO(2), > 5%) in each subject. Finally, baseline FEV(1) and changes in FEV(1) as a percentage of baseline values were recorded in all subjects. RESULTS: We found that baseline and fall SaO(2) values for the three groups were similar. However, in each group a significant mean change in SaO(2) was evident during sputum production (asthmatic patients, 6.0%; smokers, 5.3%; healthy subjects, 6.0%). Moreover, the mean durations of mild desaturation were 7 min, 21 s in asthma patients; 8 min, 24 s in smokers; and 7 min, 16 s in healthy subjects. Similarly, the durations of marked desaturation were 1 min, 25 s in asthmatic patients, 1 min, 19 s in smokers, and 1 min, 21 s in healthy subjects. The mean (+/- SD) fall in FEV(1) was not statistically different among the three groups (asthmatic patients, 1.36 +/- 5.6%; smokers, 7.58 +/- 11.76%; and healthy subjects, 0.05 +/- 9.6%). However, one smoker did experience excessive bronchoconstriction (fall in FEV(1), > 20%). CONCLUSIONS: This study demonstrated a significant and comparable fall in SaO(2) during sputum induction by inhalation of hypertonic saline solution in asthmatic patients, smokers, and healthy subjects. The results suggest that subjects who are hypoxemic before sputum induction require SaO(2) monitoring during the procedure.
Adolescent↗
Heat shock protein 70 upregulation is related to HLA-DR expression in bronchial asthma. Effects of inhaled glucocorticoids.
BACKGROUND AND OBJECTIVE: Antigen processing determines the production of peptides from antigens - including allergens - and their binding to class II major histocompatibility complex molecules, that stimulate T-cell responses. Heat shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic peptides and in facilitating class II peptide assembly. We studied the HLA-DR and hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as the effect of low dose fluticasone propionate treatment. METHODS: Twenty-three asthmatics and eight normal subjects were selected. In each subject BAL and bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 microg b.d.) in a placebo-controlled double-blind study. BAL fluid and biopsies were processed to evaluate HLA-DR and hsp70 expression by immunochemistry methods. RESULTS: Hsp70 and HLA-DR upregulation was present on professional and non-professional antigen presenting cells (APCs). In asthmatics, the hsp70 and HLA-DR expression was higher in BAL (hsp70 P<0.001, HLA-DR P<0.001) and bronchial epithelium (hsp70 P<0.001, HLA-DR P<0.001) when compared with controls. We also observed a significant correlation between hsp70 and HLA-DR expression in BAL (P<0.005) and epithelium (P<0.001). Fluticasone propionate treatment down-regulated the hsp70 and HLA-DR expression in BAL (hsp70 P < 0.001, HLA-DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA-DR P < 0.05). A serial section comparison study showed that CD1a+ cells and macrophages were positive for both hsp70 and HLA-DR in the submucosa. CONCLUSIONS: Our results support the hypothesis that hsp70 over-expression implies a potential role for these proteins in antigen processing and/or presentation resulting in an increased activity of APCs, which is essential for the initiation and modulation of the asthmatic immune response in chronic asthma. Fluticasone propionate induces downregulation of HLA-DR and hsp70 molecules thus regulating inflammation by affecting key mechanisms of the allergic response.
Administration, Inhalation↗
Personality profiles and breathlessness perception in outpatients with different gradings of asthma.
We studied the relationship between personality profiles, breathlessness perception and clinical and functional features in 36 outpatient asthmatics (12 females; age range: 18-52 yr). Each patient underwent psychometric evaluation with Minnesota Multiphasic Personality Inventory (MMPI). Breathlessness perception was evaluated by Borg's scale during methacholine (M) challenge, and PS20 (the perception score obtained when FEV1 fell by 20%) was recorded. Baseline FEV1 values ranged from 70.0 to 126%. PC20 M values ranged from 0.05 to 31.7 mg/ml. According to a symptoms score system (0 to 12 points), 12 asthmatics were classified as mild, 12 as moderate, and 12 as moderate/severe. We did not find any specific personality profile in asthmatic patients. Sixteen asthmatics had at least one MMPI subscale score indicative of psychological disturbances. We found a significant trend from mild to moderate and moderate/severe asthmatics (p < 0.015), when the number of asthmatics with subscale scores indicative of psychological disturbances was compared to that of asthmatics with normal scores. Moreover, we found that the asthmatics with scores indicative of hypochondriasis showed a significant trend from mild to moderate and moderate/severe asthma (p < 0.015). Furthermore, in all asthmatic patients, hypochondriasis scores were positively correlated to asthma severity score (p < 0.02). PS20 values ranged from 0.1 to 8.1. Twelve asthmatics were hypoperceivers (PS20 < or = 1) and four were hyperperceivers (PS20 > or = 5). We observed a significant trend from mild to moderate and moderate/severe asthmatics (p < 0.025) when we compared the number of hypoperceivers to that of normoperceivers. In conclusion, we found that in outpatients with different grading of asthma, severity of disease is linked to psychological disturbances and poor perception of breathlessness, additionally, hypochondriasis was related to disease severity in all patients.
Adolescent↗
Eosinophils, mast cells, and basophils in induced sputum from patients with seasonal allergic rhinitis and perennial asthma: relationship to methacholine responsiveness.
OBJECTIVES: We attempted to determine whether inflammation is present in induced sputum of patients with seasonal allergic rhinitis (AR) as compared with those with perennial asthma (AS) and examined its relationship with bronchial responsiveness to methacholine. METHODS: Sputum was induced in 30 patients with seasonal rhinitis in response to grass pollens only and in 15 patients with stable, asymptomatic asthma. The AR group was divided according to methacholine PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24 micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.2 and 19.6 micromol. In the AS group, methacholine PD20 ranged between 0.42 and 2.6 micromol. The percentage of eosinophils and metachromatic cells (alcian blue-positive) was assessed in sputum by light microscopy. Tryptase-positive cells and EG2+ cells were identified by immunocytochemistry with the mouse anti-human mast cell-tryptase monoclonal antibody and the monoclonal anti-eosinophil cationic protein antibody. RESULTS: We found that the number of eosinophils in the AS group was greater than that in the AR+ group (p < 0.05) and in the AR- group (p < 0.01). Moreover, the eosinophil count was lower in the AR- group compared with the AR+ group (p < 0.05). Similarly, the number of EG2+ cells was greater in the AS group than in the AR group (p < 0.02) and the AR- group (p < 0.05). Moreover, the EG2+ cell count was lower in the AR- group than in the AR+ group (p < 0.05). The number of mast cells and basophils in the AS group was greater than that in the AR group (p < 0.05 and p < 0.01, respectively). Mast cells in sputum were tryptase-positive. Basophils were present in sputum from 23% of patients with AR and 53% of patients with asthma. There was a significant correlation between methacholine PD20 and eosinophils (p < 0.005) and mast cells (p < 0.02) but not with basophils in those patients showing a measurable methacholine PD20 (AR+ and AS groups). CONCLUSIONS: Inflammatory cells are present not only in the airways of patients with asthma but also in airways of patients with seasonal AR, even outside natural exposure. Moreover, we provide evidence for the presence of basophils in sputum of patients with asthma even during clinical remission. The presence of bronchial responsiveness is associated with an increase in the number of eosinophils and metachromatic cells. Our findings are consistent with the hypothesis that eosinophils, as well as mast cells, contribute to bronchial responsiveness not only in AS but also in seasonal AR.
Adult↗
Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study.
In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.
Administration, Inhalation↗
Airways remodeling is a distinctive feature of asthma and is related to severity of disease.
PURPOSE: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS: Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS: We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.
Adolescent↗