Lorenza Melosini

Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases

Background. Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary oxidative stress biomarkers such as malondialdehyde (MDA). Subjects and Methods. We measured MDA levels in EBC in a large number of patients (N = 194) with respiratory diseases: asthma (N = 64), bronchiectasis (BE, N = 19), chronic obstructive pulmonary disease (COPD, N = 73), idiopathic pulmonary fibrosis (IPF, N = 38). Fourteen healthy nonsmoking subjects were included as controls. Results. Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV1% (rho:  −0.24, P < .05). Conclusions. EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV1 reduction.

Asthma Control Test (ACT): Comparison with Clinical, Functional, and Biological Markers of Asthma Control.

Background. Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV1). Objective. To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation. Methods. A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV1 before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card. Results. ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV1, FEV1 reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment. Conclusion. ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.

Comparison between Airway Responses to High versus Low Molecular Weight Compounds in Occupational Asthma

Occupational asthma (OA) is a heterogeneous disease, and the characteristics of the sensitizer responsible for OA may induce different clinical, functional, and biological manifestations. We examined the characteristics of 74 patients with OA induced by low molecular weight compounds (LMWC) or by high molecular weight compounds (HMWC) and diagnosed by specific inhalation challenge (SIC). Patients with OA induced by LMWC had a longer occupational exposure before the beginning of symptoms, a lower sputum eosinophilia, and a higher prevalence of late airway response (LAR), in comparison with patients with OA induced by HMWC. Pulmonary function tended to be poorer and atopy tended to be less frequent in LMWC-induced OA than in HMWC-induced OA. These data confirm and extend previous observations showing that the characteristics of the specific sensitizer inducing OA may determine different clinical, functional, and biological features, probably related to the difference pathogenetic mechanisms underlying these different types of OA.

Evaluation of underreporting tuberculosis in Central Italy by means of record linkage

BackgroundTuberculosis (TB) surveillance systems have some pitfalls outside of a National Tuberculosis Program and lack of efficient surveillance hampers accurate epidemiological quantification of TB burden.In the present study we assessed the quality of surveillance at the University Hospital in Pisa (UHP), Italy, and TB incidence rates over a ten year period (1999–2008).MethodsAssessment of underreporting was done by record-linkage from two sources: databases of TB diagnoses performed in the UHP and the Italian Infectious Disease Surveillance (IIDS) system. Two different databases were examined: a) TB diagnoses reported in the Hospital Discharge Records (HDR) from three Units of UHP (Respiratory Pathophysiology, Pulmonology and Infectious Diseases Units) (TB database A); b) TB diagnoses reported in HDR of all Units of UHP plus TB positive cases obtained by the Laboratory Register (LR) of UHP (TB database B). For the TB database A, the accuracy of TB diagnosis in HDR was assessed by direct examination of the Clinical Record Forms of the cases. For the TB database B, clinical and population data were described, as well as the trend of incidence and underreporting over 10 yrs.ResultsIn the first study 293 patients were found: 80 patients (27%) with a confirmed TB diagnosis were underreported, 39 of them were microbiologically confirmed. Underreporting was related to age (Reported vs Non Reported, mean age: 49.27 ± 20 vs 55 ± 19, p < 0.005 ), diagnosis (smear positive vs negative cases 18.7 vs 81.2%, p = 0.001), microbiological confirmation (49% vs 51%, p < 0.05), X-ray findings (cavitary vs non-cavitary cases: 12.5 vs 87.5%, p = 0.001) but not to nationality.In the second study, 666 patients were found. Mean underreporting rate was 69.4% and decreased over time (68% in 1999, 48% in 2008). Newly diagnosed TB cases were also found to decrease in number whereas immigration rate increased. Underreporting was related to nationality (Immigrants vs Italians: 18% vs 68%, p < 0.001), diagnosis (microbiological confirmation: 25% vs 75%, p < 0.01), kind of hospital regimen (hospitalized patients vs Day Hospital: 70% vs 16%, p < 0.001), and position of TB code in the HDR (TB code in first position vs in the following position: 39,5% vs 45% p < 0.001).ConclusionsTB is underreported in Pisa, particularly in older patients and those without microbiological confirmation. The TB code in first position of HDR seems fairly accurate in confirming TB diagnosis.

May the Reduction of Exposure to Specific Sensitizers Be an Alternative to Work Cessation in Occupational Asthma? Results from a Follow-Up Study

Background: Few data are reported on the effects of a reduction of exposure to specific sensitizers in occupational asthma (OA). The objective of this study was to evaluate the clinical outcome of subjects with OA, comparing the effect of a reduction with that of the persistence or cessation of occupational exposure to the specific sensitizer. Subjects and Methods: Forty-one subjects with OA due to different sensitizers were diagnosed via a specific inhalation challenge. After a follow-up interval of 3.5 years, subjects were reexamined by clinical assessment, bronchial hyperresponsiveness (BH) and induced sputum. Results: At follow-up, subjects who had reduced occupational exposure (n = 22) showed a significant improvement in BH and a nonsignificant improvement in sputum eosinophilia (from 5.3 to 1.1%, n.s.), while subjects still exposed (n = 10) showed a significant decrease in FEV1. Subjects who ceased work (n = 9) showed a trend of improvement in BH and sputum eosinophilia. Logistic analysis showed that the major determinant of improvement in BH at follow-up was the severity of BH at diagnosis, with a minimal contribution from the duration of exposure and treatment with inhaled corticosteroids during follow-up; reduction of work exposure did not enter into any model. Conclusion: The reduction of occupational exposure could not be considered to be as effective as work cessation, which remained the best treatment for OA. However, it was not associated with a deterioration of FEV1 as observed in subjects with persistent exposure.

Intracellular detection of interleukin 17 and other cytokines in human bronchoalveolar lavage fluid: A first assessment

Increasing evidence links pulmonary pathology to cytokines determining an inflammatory environment in the lung. Detection of cells secreting specific cytokines in BALF could be helpful as a diagnostic tool but which cytokines to choose among their great variety may be the first question to solve. The aim of this study was to investigate the Th1, Th2 and Th17 cytokine profile in whole cells within the human bronchoalveolar lavage fluid (BALF) by flow cytometry, with a focus on interleukin (IL)-17-producing cells, in order to assess which cytokines might lend themselves as markers of disease in future studies. BALF and paired peripheral blood samples were collected from 52 patients admitted to hospital for pulmonary pathologies. Cells obtained from BALF and peripheral blood were incubated in vitro in the absence or presence of appropriate stimuli and analyzed for intracellular content of IL-4, -10, -12, -17, interferon (IFN)γ and tumor necrosis factor (TNF)α in association to expression of either HLA-DR or CD4. IL-17-secreting cells were further characterized. Production of IL-17 by unstimulated BALF cells could be detected in 2 of the 32 patients that could be examined; upon PMA/IM stimulation in vitro, IL-17 was produced by varying percentages of lymphocytes, mostly memory CD4(+) cells, in all BALF samples. IL-4 could be detected in a relatively high proportion of unstimulated HLA-DR(+/-), SSC(hi) cells, most probably granulocytes; IL-10 could be found mostly in macrophages in a number of the BALF samples analyzed. Finally, IFNγ and TNFα were only produced by lymphocytes after in vitro stimulation. This study shows that T cells producing IL-17 can be found in the lung of respiratory patients in the absence of ex vivo stimulation, making IL-17 a good candidate marker of specific pathologies of the lung. Upon stimulation, IL-17 production was accounted for by CD4(+) CD45RO(+) cells. Other cytokines are also discussed. An interesting cytokine secretion profile found in BALF from a patient with rheumatoid lung disease is also reported.