Alessandro Fois

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20–44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991–1993; n=6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998–2000; n=18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007–2010; n=10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19–1.59) from 1998–2000 to 2007–2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Bacterial Community Acquired Pneumonia in HIV-Infected Inpatients in the Highly Active Antiretroviral Therapy Era

Introduction:Highly active antiretroviral therapy (HAART) has deeply modified HIV/AIDS related morbidity and mortality. However, bacterial community acquired pneumonia (BCAP) still represents one of the most frequent causes of morbidity in HIV-infected patients with an inpatient 10% mortality rate.Objectives:We retrospectively studied the characteristics of BCAP in consecutive HIV-infected inpatients hospitalized from 1999 to 2004 and evaluated the presence of risk factors and the influence of combination antiretroviral therapy receipt on BCAP outcomes.Results:We studied 84 BCAP episodes in 76 HIV-infected inpatients (63 males and 13 females) aged 27–80 years. Thirty-two (42.1%) patients were receiving combination antiretroviral treatment (CART) while 44 (57.9%) were not treated (NART). BCAP incidence progressively increased from 1999 to 2004. The overall percentage of injection drug users was > 84%, of smokers > 88% and alcohol abusers > 32% with no statistical difference between CART and NART. Streptococcus pneumoniae was the most frequently identified pathogen (60%). Time to clinical stability was significantly longer in NART in respect of CART (p = 0.011). In multivariate analysis, CDC stage C, CD4 cell count < 100 × 106 cells/l, and S. pneumoniae etiology were predictors for time to clinical stability > 7 days, while receipt of antiretroviral therapy was protective. The percentage of deaths did not differ between CART and NART; most patients had a CD4 count < 200 × 106 cells/l or severe concomitant diseases.Conclusions:The incidence of BCAP was high in HIV-infected inpatients observed in the present study mainly due to HIV infection itself, IVDU, alcohol abuse and smoking habit. A longer time to clinical stability was associated with advanced HIV infection and with S. pneumoniae etiology, while receipt of antiretroviral therapy was protective. Injection drug abuse treatment, alcohol abuse and smoking cessation programs, antiretroviral treatment adherence support and pneumococcal vaccination should be implemented to reduce the incidence and to improve the outcomes of BCAP in HIV-infected patients.

Simultaneous detection of N-acetyl-l-cysteine and physiological low molecular mass thiols in plasma by capillary electrophoresis

N-acetyl-l-cysteine (NAC) is a therapeutic drug widely used as mucolytic agent in the treatment of respiratory diseases. Recently it has been proposed that NAC administration may modify the plasma levels of low molecular weight thiols (LMW) like cysteine, homocysteine and glutathione, though it has been still debated if their plasma concentration increases or decreases during the therapy. Therefore research calls for methods able to analyze simultaneously NAC and the other plasma LMW thiols in order to evaluate if NAC is able to modify plasma thiols concentration and in particular to reduce homocysteine levels in hyperhomocysteinemia. In this paper we present a new capillary electrophoresis method that allows a baseline separation of plasma NAC from the physiological thiols. The proposed method has been utilized to measure the drug and the physiological LMW thiols in NAC administered chronic obstructive broncho-pneumopathy (COPB) disease patients.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

Adult eczema in Italy: prevalence and associations with environmental factors.

Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking.

Circulating biomarkers of oxidative stress in chronic obstructive pulmonary disease: a systematic review

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking. Increased oxidative burden plays an important role in the pathogenesis of COPD. There is a delicate balance between the toxicity of oxidants and the protective function of the intracellular and extracellular antioxidant defense systems, which is critically important for the maintenance of normal pulmonary functions. Several biomarkers of oxidative stress are available and have been evaluated in COPD. In this review, we summarize the main literature findings about circulating oxidative stress biomarkers, grouped according to their method of detection, measured in COPD subjects.

Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study

The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid.

Tuberculosis Screening before Anti–Hepatitis C Virus Therapy in Prisons

To the Editor: Prisons represent a crucial setting for tuberculosis (TB) control. Worldwide, reported TB rates for correctional system populations have been 10–100× higher than rates for the local civilian populations, and TB outbreaks with a high number of TB multidrug-resistant cases have been documented (1,2). Prisons are known as social and sanitary pathology reservoirs in which TB is often associated with chronic infectious diseases caused by HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) (2). HCV prevalence among inmates is 30%–40% (range 2%–58%), which is higher than that in the general population and is related to injection drug use (3). For these reasons, effective anti-HCV therapeutic approaches are recommended by national and international guidelines for decreasing illness, death rates, and reservoirs of infection in prisons (4,5). The standard of care for patients with chronic hepatitis C infection is represented by pegylated interferon-α (Peg-IFN) and ribavirin. These drugs determine complex antiviral, immunomodulatory, and antiproliferative actions, which can cause serious side effects such as leukopenia/neutropenia and alterations in the cytokine network (3). Although severe cellular immunodeficiency can often facilitate the development of many infections, only 4 clinical cases of TB in patients undergoing HCV antiviral therapy have been described in the literature (6–8), and only 1 of these was clearly described as a TB reactivation (7). We describe a case of pulmonary TB reactivation during therapy with Peg-IFN and ribavirin in a 44-year-old white male inmate, affected by genotype 1b/4a chronic hepatitis C. After prison admission in 2009, he underwent routine screening tests for infectious diseases, which indicated HCV antibody, HBV surface antibody, HBV core IgG antibody, and tuberculin skin test positivity. Results of chest radiograph and HIV screening were negative. His previous history involved injection drug use, smoking, and alcohol consumption. Anti-HCV therapy of directly observed administration of Peg-INF α-2a (180 µg/wk) and ribavirin (1,200 mg/d) was started. During therapy, the patient had only mild musculoskeletal pain and temporary irritability. During the 12th week of treatment, HCV-RNA decreased by 1 log10; therefore, the ribavirin dose was increased to 1,600 mg per day. Even after the therapy modification, no virologic suppression was found. Although during the 33rd week of therapy the patient had weakness, cough, and 2 episodes of hemoptysis, the results of a physical examination were unremarkable. Therapy was immediately discontinued. Sputum specimens collected on 3 consecutive days were positive for acid-fast bacilli. Nucleic acid amplification assays and cultures performed on mycobacteria growth indicator tube (Bactec MGIT; Becton Dickinson, Franklin Lakes, NJ, USA) and on Lowenstein-Jensen medium were positive for Mycobacterium tuberculosis isolates that later showed sensitivity to streptomycin, isoniazid, rifampin, and ethambutol. The patient was isolated at the Institute of Respiratory Diseases, University of Sassari–Faculty of Medicine, Sassari, Italy. A chest radiograph showed opacity in the upper right lung, and a high-resolution computed tomography scan (Figure) showed multiple lesions that were considered compatible with TB. CD4+ cell count (52.4%; 669 cells/mm3) was within reference range. Figure Computed tomography image of chest of patient with tuberculosis after anti–hepatitis C virus therapy. A parenchymal distortion 32 mm in diameter is shown in the upper right lung with initial central excavation 10 mm in diameter. Similar lesions ... TB treatment with rifampin, isoniazid, pyrazinamide, and ethambutol with pyridoxine was started. After 4 weeks of therapy, 3 sputum specimens were negative for acid-fast bacilli, but a bacterial culture was still positive; mycobacteria indicator growth tube culture was negative after 5 weeks. The interaction process between the IFN-α/β system and M. tuberculosis is not well known; nevertheless, Peg- IFN, alone and in combination with ribavirin, is considered potentially immunosuppressive (4,9). Immunodeficiency caused by Peg-IFNs and ribavirin may cause lower leukopenia/lymphopenia values than expected during anti-HCV treatment and may also lower CD4+ cell count and function (10). In the patient reported here, CD4+ cell count was within the reference range, and lung TB with excavations developed after 34 weeks of therapy. Before TB diagnosis, the patient had not shown any signs or symptoms of other infections and had not mentioned serious adverse effects from Peg-IFN and ribavirin treatment. However, the initial symptoms of TB and the common side effects of Peg-IFN therapy can be similar, which could have led to a delay in the diagnosis of TB. In conclusion, even if only a few cases of active TB have been reported in the literature, it is well known that standard anti-HCV treatment increases the risk for infections. A high proportion of patients with positive purified protein derivative results, isolation of >30% of multidrug-resistant strains of M. tuberculosis, and high prevalence of HCV antibody are concomitant among inmates. These data, together with current recommendations for increasing use of Peg-IFN and ribavirin in marginalized populations in correctional facilities, show the need to consider TB risk before starting HCV antiviral therapy. The management of simultaneous HCV and M. tuberculosis infections in prisons presents particular difficulties and pitfalls to overcome. In prisons, the clinical history of inmates should be carefully evaluated, a tuberculin skin test or Quantiferon TB in Tube test (Cellestis, Melbourne, Australia) should be performed, and, if those results are positive, a chest radiograph should be taken. Before receiving Peg-IFN, purified protein derivative–positive patients should receive anti-TB chemoprophylaxis. The case described here underscores the need for a careful and multidisciplinary evaluation of inmate patients for latent TB before administration of Peg-IFN and ribavirin therapy, thus avoiding reactivation.

Plasma protein thiols: an early marker of oxidative stress in asthma and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n = 24) and mild stable COPD (n = 29) and in age‐ and sex‐matched controls. Forced expiratory volume in 1 s (FEV1) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (ρ = 0·49, P = 0·007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR = 0·32, 95% CI 0·13–0·78, P = 0·01) and COPD (OR = 0·50, 95% CI 0·26–0·95, P = 0·03). These findings suggest that proteins ‐SH are a sensitive OS marker in early COPD and asthma.

The impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities: a population-based observational study.

BackgroundChronic respiratory diseases are a significant cause of morbidity and mortality worldwide. We sought to evaluate the impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities in adults.MethodsIn the Gene Environment Interactions in Respiratory Diseases study (2007/2010), a screening questionnaire was mailed to 9,739 subjects aged 20–44 (response rate: 53.0%) and to 3,480 subjects aged 45–64 (response rate: 62.3%), who were randomly selected from the general population in Italy. The questionnaire was used to: identify the responders who had asthma, chronic bronchitis, allergic rhinitis or asthma-like symptoms/dyspnoea/other nasal problems; evaluate the total burden [use of hospital services (at least one ED visit and/or one hospital admission) and number of days with reduced activities (lost working days and days with limited, not work related activities) due to any health problems (apart from accidents and injuries) in the past three months]; evaluate the contribution of breathing problems to the total burden (hospitalizations and number of days with reduced activities specifically due to breathing problems).ResultsAt any age, the all-cause hospitalization risk was about 6% among the subjects without any respiratory conditions, it increased to about 9-12% among the individuals with allergic rhinitis or with asthma-like symptoms/dyspnoea/other nasal problems, and it peaked at about 15-18% among the asthmatics with chronic bronchitis aged 20–44 and 45–64, respectively. The expected number of days with reduced activities due to any health problems increased from 1.5 among the subjects with no respiratory conditions in both the age classes, to 6.3 and 4.6 among the asthmatics with chronic bronchitis aged 20–44 and 45–64, respectively. The contribution of breathing problems to the total burden was the highest among the asthmatics with chronic bronchitis (23-29% of the hospitalization risk and 39-50% of the days with reduced activities, according to age).ConclusionsThe impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities is substantial, and it is markedly different among adults from the general population in Italy. The contribution of breathing problems to the total burden also varies according to the respiratory condition.