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Maria De Santis,
Rosanna Inzitari,
Silvia L Bosello,
Giusy Peluso,
Chiara Fanali,
Federica Iavarone,
Gaetano Zizzo,
Mario Bocci,
Tiziana Cabras,
Irene Messana,
Leo Fuso,
Francesco Varone, Gabriella Pagliari,
Massimo Castagnola,
Gianfranco Ferraccioli
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ABSTRACT: β-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters.
β-thymosins concentrations were determined by reverse phase-high performance liquid chromatography-electrospray-mass spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls.
Thymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis.
We describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.
Respiratory research 02/2011; 12:22. · 3.36 Impact Factor
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Maria De Santis,
Silvia Laura Bosello,
Giusy Peluso,
Michela Pinnelli,
Stefano Alivernini,
Gaetano Zizzo,
Mario Bocci,
Annunziata Capacci,
Giuseppe La Torre,
Alice Mannocci, Gabriella Pagliari,
Francesco Varone,
Roberto Pistelli,
Francesco Maria Danza,
Gianfranco Ferraccioli
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ABSTRACT: So far no clinical or experimental evidences clearly explain how and which systemic sclerosis (SSc) patients will experience a functional and radiological progression of interstitial lung disease (ILD).
The aim of the study was to investigate whether any bronchoalveolar lavage fluid (BALF) characteristic, compared with clinical, functional and radiological parameters, is associated with the risk of progression of ILD and worse survival in SSc patients.
Lung involvement was evaluated in 110 consecutively examined SSc patients with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT); 73 patients with evidence of ILD on HRCT underwent BAL. The progression of ILD was evaluated with PFTs and HRCT after 1-year follow-up. A 36-month survival analysis was assessed.
ILD patients with alveolitis had a higher risk to have restrictive lung disease and honeycombing, to experience a worsening in honeycombing score or to develop honeycombing. ILD progression was associated with the evidence of honeycombing on HRCT, with the presence of eosinophils, with an inverted CD4/CD8 ratio and with a higher CD19 percentage count in the BALF or with a positive BALF microbiological culture. The patients with ILD had a worse overall survival. The diffuse disease was the only independent risk factor of overall mortality, and the extent of honeycombing on HRCT was the only independent risk factor of lung disease-related mortality.
Our study suggests the importance of evaluating ILD with HRCT and BAL in order to characterize the risk factors of SSc lung involvement progression.
The Clinical Respiratory Journal 11/2010; 6(1):9-17. · 1.06 Impact Factor
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ABSTRACT: Some studies have raised the question of the need for chronic controller therapy in mild persistent asthma as suggested by international guidelines. Although the Improving Asthma Control (IMPACT) and Beclomethasone plus Salbutamol (BEST) studies suggest that on-demand therapy in some patients with mild persistent asthma achieves a similar degree of asthma control based on symptoms and functional outcomes, the IMPACT study indicates that regular and on-demand therapy is not equivalent for controlling airway inflammation. Persistent airway inflammation might lead to airway remodelling with onset or worsening of symptoms, deterioration in lung function, and reduced response to pharmacological therapy. However, the relationships between chronic airway inflammation and airway remodelling need to be clarified. Choosing the 'right' pharmacological strategy (regular versus on-demand treatment) for asthma control is currently difficult due to the fact that (1) inflammatory outcome measures were not generally incorporated into asthma clinical trials; (2) the relationships between chronic airway inflammation and airway remodelling are largely unknown; (3) current clinical asthma trials that are generally based on symptomatic and functional outcome measures are too short to assess the impact of regular anti-inflammatory therapy on natural history of asthma; (4) asthma is an heterogeneous disease and different phenotypes of asthma patients likely requiring a different therapeutic approach can be identified, even in the same class of asthma severity. Guidelines for asthma management are valuable tools, although they are necessarily based on a strategy directed to the best outcome in a group of patients. Asthma phenotyping is becoming central for asthma management. The issue of regular versus on-demand treatment of intermittent and mild persistent asthma would be better addressed if considered within an individualized approach to asthma management and assessment. Identification of clinical, functional, morphological and biochemical phenotypes of patients with asthma and its clinical implications is likely to lead to a tailored, individualized, pharmacological therapy and asthma management.
Therapeutic Advances in Respiratory Disease 09/2009; 3(4):175-91.
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ABSTRACT: A progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients.
100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6-12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices.
90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54-64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40-34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure > or = 40 mmHg was found in 6 (37.5%) patients with alveolitis.
We found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL would be necessary to detect any infections of the lower respiratory tract that may cause further deterioration in lung function.
Respiratory research 01/2005; 6:96. · 3.36 Impact Factor
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ABSTRACT: An iCycler iQ real-time PCR assay targeting 18S rRNA Aspergillus-specific sequences was developed for the diagnosis of invasive pulmonary aspergillosis (IPA). Positive findings were obtained for 18 of 20 (90%) bronchoalveolar lavage (BAL) fluid specimens from patients with probable or confirmed IPA and were obtained for none of the 24 BAL samples from patients with no clinical evidence of aspergillosis. These results were concordant with those of a nested PCR assay, which detected 90% of the patients with IPA, while galactomannan ELISA revealed positivity for 100% of these patients, suggesting that combined use of methods might improve the diagnosis of IPA.
Journal of Clinical Microbiology 09/2003; 41(8):3922-5. · 4.15 Impact Factor
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Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 04/2003; 20(1):75-6. · 1.27 Impact Factor
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ABSTRACT: Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimer's disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p </= 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.
Journal of Neurology 03/2003; 250(3):325-32. · 3.47 Impact Factor
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ABSTRACT: Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD)
and Alzheimer's disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal
subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level
underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects
and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic
COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of
anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher
than AD patients (p ≤ 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and
deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated
with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected
neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with
the worsening of the hypoxemia.
Journal of Neurology 02/2003; 250(3):325-332. · 3.47 Impact Factor
