Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma.

BACKGROUND: There is increasing evidence to support a role for total mast cells (MC(TOT)) in the vascular component of airway remodeling in asthma. On the contrary, up to now, no study has addressed the role of chymase-positive mast cells (MC(TC)) in microvasculature changes. OBJECTIVE: We sought to assess the role of MC(TC) in the vascular component of airway remodeling in asthma. METHODS: We recruited 8 patients with mild-to-moderate asthma and 8 healthy volunteers as a control group. Fiberoptic bronchoscopy with endobronchial biopsy was successfully performed in all subjects. Immunostaining was performed for quantification of vessels, vascular endothelial growth factor (VEGF)-positive cells, MC(TOT), and MC(TC). RESULTS: Compared with those from healthy subjects, endobronchial biopsy specimens from asthmatic patients showed increased numbers of MC(TOT) and MC(TC) and VEGF(+) cells (P < .05). In asthmatic patients the number of vessels and the vascular area was also greater than in healthy subjects (P < .05). Additionally, in asthmatic patients the number of MC(TC) was significantly related to the vascular area (r(s) = 0.74, P < .01) and to the number of VEGF(+) cells (r(s) = 0.78, P < .01). Moreover, a colocalization study revealed that MC(TC) were a relevant cellular source of VEGF. Finally, a 6-week treatment with inhaled fluticasone propionate was able to reduce MC(TC) numbers. CONCLUSION: MC(TC) can play a role in the vascular component of airway remodeling in asthma, possibly through induction of VEGF. CLINICAL IMPLICATIONS: Specific targeting of MC(TC) might be a tool for treating vascular remodeling in asthma.

Changes in lung function and respiratory muscle strength after sternotomy vs. laparotomy in patients without ventilatory limitation.

A relevant ventilatory defect occurs after sternotomy, a very common thoracic surgical opening. The mechanism of the ventilatory impairment is unclear. Moreover, until now, the effect of sternotomy on pulmonary gas exchange has scarcely been investigated. We evaluated the time-course up to recovery and changes in spirometry, maximum static inspiratory (PI(max)) and expiratory (PE(max)) mouth pressures and pulmonary gas exchange in 6 patients after sternotomy and in 8 patients after laparotomy. All patients were free of cardiopulmonary diseases and had normal preoperative lung function. Sternotomy and laparotomy decreased forced vital capacity (FVC) by 67 and 49%, respectively. Moreover, the percent decreases in PI(max), PE(max) and PaO(2) after sternotomy vs. laparotomy were respectively 54 vs. 57%, 54 vs. 60%, and 22.6 vs. 7.5% (p < 0.05). Following sternotomy, the percent decreases in FVC correlated with the percent decreases in PI(max) (p < 0.05) and PE(max) (p < 0.01). The return to baseline values occurred after approximately 2 weeks. The present study shows that sternotomy can induce greater respiratory effects than laparotomy and suggests a relevant involvement of respiratory muscle weakness after surgical opening of the thorax. The study also supports the view that the evaluation of patient's lung function before sternotomy can be clinically relevant.

The lung in immune-mediated disorder: rheumatoid arthritis.

Various pleuro-pulmonary abnormalities are known to complicate vascular collagen diseases, particularly, rheumatoid arthritis. Each component of the respiratory system is affected, either separately or in combination. Although most pulmonary complications appear in an established case of collagen vascular disease, in certain conditions, the lung disease precedes the more typical manifestation. While some complications are asymptomatic and tend to be resolved spontaneously (for e.g. pleuritis and rheumatoid nodules), others may cause severe or fatal conditions (interstitial pneumonia and constrictive bronchiolitis). The incidence of interstitial lung disease is increasing in vascular collagen disease. This may be mainly attributed to the increase use of invasive techniques such as bronchoscopy and video-assisted thoracoscopic surgery and in part due to the use of high resolution computed tomography, and functional pulmonary tests.

Induced sputum and bronchoalveolar lavage from patients with hypersensitivity pneumonitis.

BACKGROUND AND AIM: Hypersensitivity pneumonitis (HP) is an immunologically induced inflammation of the lung parenchyma, though bronchial airways may be also involved. The aim of this study was to compare the cellular profiles of induced sputum (IS) in patients with newly diagnosed HP to that of healthy subjects, and to examine the relationship between inflammatory cells from IS and BAL. METHODS: Nine HP patients and 9 healthy volunteers were studied. IS was obtained by inhalation of hypertonic saline solution in all subjects. Bronchoscopy was performed on a different occasion in all patients and in five controls. RESULTS: IS was well tolerated and preferred to BAL by all subjects. Both IS and BAL from HP patients showed a significant increase in total cells (P < 0.02 and P < 0.001) and in lymphocytes (P < 0.02 and P < 0.001) and a significant decrease in macrophages (P < 0.05 and P < 0.001), when compared with normal subjects. In HP patients, total cells number in IS was higher than that in BAL (P < 0.02). Moreover, the percentage of lymphocytes was significantly lower in IS than in BAL (P < 0.001). No significant relationship was found between total cells or inflammatory cells from IS and the corresponding ones from BAL and wide limits of agreement were found between lymphocytes from IS and BAL. CONCLUSIONS: This study demonstrated that both BAL and IS from newly diagnosed HP patients contained significantly more total cells and lymphocytes, when compared to healthy subjects. Moreover, differential cell counts in HP patients showed that IS and BAL reflected different compartments of inflammation. Thus, IS could represent a complementary, but not alternative tool to bronchoscopy both in research and in the clinical monitoring of HP patients.

Assessment of breathlessness perception by Borg scale in asthmatic patients: reproducibility and applicability to different stimuli.

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from -2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patient's breathlessness perception by this technique in clinical settings and in the physiology laboratory.

Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone.

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.