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Biomedical subjects

L Richeldi

Publications and source records attributed to L Richeldi.

At least 19 recordsLinked to original sources
PubMed2005

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobic and antiinflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials up to May 2005. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. The full text of any potentially relevant article was reviewed independently by two reviewers. MAIN RESULTS: Seven studies recruiting a total of 416 participants met the inclusion criteria. The quality of reporting of study methodology was generally low. We assembled findings from studies comparing macrolide treatment for at least 4 weeks in adult and pediatric patients treated for chronic asthma. Four studies showed a positive effect on symptoms of macrolides in different types of asthmatic patients. There were limited data available for meta-analysis. There was no significant difference in FEV1 for either parallel or crossover trials. However, there were significant differences in eosinophilic inflammation and symptoms. One large parallel group trial reported significant differences in peak flow but these differences abated within six months of treatment. AUTHORS' CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗
PubMed2005

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobic and antiinflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials up to May 2004. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. The full text of any potentially relevant article was reviewed independently by two reviewers. MAIN RESULTS: Seven studies recruiting a total of 416 participants met the inclusion criteria. The quality of reporting of study methodology was generally low. We assembled findings from studies comparing macrolide treatment for at least 4 weeks in adult and pediatric patients treated for chronic asthma. Four studies showed a positive effect on symptoms of macrolides in different types of asthmatic patients. There were limited data available for meta-analysis. There was no significant difference in FEV1 for either parallel or crossover trials. However, there were significant differences in eosinophilic inflammation and symptoms. One large parallel group trial reported significant differences in peak flow but these differences abated within six months of treatment. AUTHORS' CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗
PubMed2005

Macrolides in the treatment of asthma and cystic fibrosis.

Asthma and cystic fibrosis are two respiratory diseases characterized by chronic inflammation, leading to remodelling of the airways. Macrolides are widely used antibiotics, with a peculiar anti-inflammatory effect. On the basis of the methodologies used by the Cochrane collaboration, this review discusses the evidence for their long-term use as anti-inflammatory agents in these two diseases. Three randomized-controlled trials (RCTs) were identified for both asthma and cystic fibrosis. A positive effect of macrolides on reducing eosinophil numbers and markers of eosinophilic inflammation was demonstrated in patients with asthma. Data on cystic fibrosis demonstrated an effect on lung function with an increase of 5.4% in forced vital capacity (FVC) in patients treated with macrolide vs. placebo, but without a significant effect on FEV1. Side-effects were rare, mild and reversible on withdrawal of treatment. Although preliminary data from small studies are promising, the role of macrolides in the treatment of these chronic disorders needs to be more firmly established with larger, well-designed trials, targeted to investigate major clinical outcomes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Management of multidrug-resistant tuberculosis in Italy.

SETTING: SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46 major clinical units and 22 laboratories nationwide in Italy. OBJECTIVES: To determine the main features, adherence to WHO guidelines and the outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled from January 1995 to December 1999. DESIGN: Observational study, preceded by proficiency testing, according to WHO recommendations. Results were stratified by appropriate and inappropriate regimens (< three active drugs). Analysis of the outcomes was performed according to adequacy of treatment. Analysis of risk factors and factors predicting treatment outcomes was performed using univariate and multivariate analysis (level of significance P < 0.05). RESULTS: One hundred and twenty-seven MDR patients were diagnosed. The overall success rate was low (39%). Seventy per cent of cases were treated with at least three active drugs. Factors predicting treatment success were new MDR-TB cases (OR 3.45; 95% CI 1.22-9.78; P < 0.05) and treatment for > or = 12 months (OR 5.03; 95% CI 1.65-15. 31; P < 0.05). Immigration and HIV infection were the main risk factors among new MDR-TB cases. CONCLUSION: The best available treatment should be provided to all newly diagnosed MDR-TB patients, avoiding the use of poorly modified regimens. MDR-TB patients should be referred to highly specialised centres.

Adult↗
PubMed2004

Corticosteroid and immunomodulatory agents in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease leading to death within a few years of diagnosis despite medical therapy. On the basis of methodologies of the Cochrane collaboration, this overview discusses the evidence for IPF therapy. Good-quality studies on oral corticosteroids, the most common medical therapy in use for IPF, are lacking. A few small studies have been carried out on the efficacy of many non-steroid immunosuppressive agents, and the results have been generally disappointing. The most extensively studied medical therapy, gamma interferon, showed a significant effect in a small randomized study, but its efficacy was not confirmed in a larger randomized-controlled trial. The long-awaited good news for patients affected by this deadly disease, and for their physicians, could come in the near future from large randomized-controlled trials with gamma interferon or other immunomodulatory agents.

Adrenal Cortex Hormones↗
PubMed2004

Triggering receptor expressed on myeloid cells: role in the diagnosis of lung infections.

The triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule, which plays an important role in myeloid cell-activated inflammatory responses. TREM-1 is expressed on blood neutrophils and monocytes, and also on alveolar macrophages, thus suggesting a potential role in lung inflammatory responses against infections. To investigate the differential expression of TREM-1 in lung infections, its levels were assessed in bronchoalveolar lavage specimens from patients with community-acquired pneumonia or tuberculosis. TREM-1 was also investigated in patients with interstitial lung diseases, as a model of noninfectious inflammatory disease of the lung. TREM-1 expression was significantly increased in lung neutrophils and in lung macrophages of patients with pneumonia (n=7; 387.9+/-61.4 and 660.5+/-18.3, respectively) compared with patients with pulmonary tuberculosis (n=7; 59.2+/-13.1 and 80.6+/-291.2) and patients with interstitial lung diseases (n=10; 91.8+/-23.3 and 123.9+/-22.8). In contrast, TREM-1 expression on peripheral blood neutrophils was no different among the three groups. In conclusion, these data suggest that triggering receptor expressed on myeloid cells-1 is selectively expressed in the lungs of patients with pneumonia caused by extracellular bacteria and not in patients with tuberculosis, providing a potential marker for differential diagnosis.

Bronchoalveolar Lavage Fluid↗
PubMed2003

Corticosteroids for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), also called cryptogenic fibrosing alveolitis (CFA), is a lethal form of diffuse lung disorder of unknown origin; the mean survival being two to four years. Currently recommended and most prescribed therapy for IPF is based on the use of systemic corticosteroids, even if no formal demonstration of efficacy of this treatment of IPF is available. Furthermore, new insights from pathological studies have produced a new hypothesis, based upon the central role played by aberrant wound healing following repeated lung injury, weakening the rationale basis of the use of corticosteroids in IPF, previously considered simply a chronic inflammatory disease. OBJECTIVES: The objective of the review was to determine the efficacy of corticosteroids in the treatment of adults with IPF. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2002), MEDLINE (January 1966 to May 2002) and EMBASE (January 1985 to December 2002) and reference lists of articles. We searched reference lists of published articles to identify trials. SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) using corticosteroids alone for the treatment of adults with IPF. DATA COLLECTION AND ANALYSIS: Abstracts of identified articles were retrieved and articles possibly fulfilling inclusion criteria were retrieved in full. Two reviewers would have independently assessed trial quality if there had been any included studies. MAIN RESULTS: Fifteen studies were selected as potentially eligible for meta-analysis. After further analysis of full text papers, no RCTs or CCTs were identified as suitable and therefore no data was available for inclusion in any meta-analysis. All studies were excluded due to inadequate methodologies. REVIEWER'S CONCLUSIONS: At present, there is no evidence for an effect of corticosteroid treatment in patients with Idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia (UIP). Given developments in understanding of the pathogenesis of IPF, randomised controlled trials designed to test the efficacy of corticosteroids will probably never be designed. As other forms of pulmonary fibrosis such as non-specific interstitial pneumonia are reported to show a better response to corticosteroids, it is crucial to make an accurate diagnosis in each patient. Moreover, therapies with immunomodulatory rather than anti-inflammatory or immunosuppressive effects may be more promising for the effective treatment of IPF/UIP.

Adrenal Cortex Hormones↗
PubMed2003

Immunomodulatory agents for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit. OBJECTIVES: To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching. SELECTION CRITERIA: RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included. DATA COLLECTION AND ANALYSIS: We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment. MAIN RESULTS: 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide. REVIEWER'S CONCLUSIONS: There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).

Azathioprine↗
PubMed2002

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobial and anti-inflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched MEDLINE, EMBASE and CINAHL up to May 2001. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. Two reviewers reviewed the full text of any potentially relevant article independently. MAIN RESULTS: The initial search retrieved 95 studies. Preliminary evaluation identified 20 studies that were potentially eligible. Five (357 patients) met the entry criteria. The entry criteria for the primary trials differed, but all recruited a specific subgroup of patients (eg severe oral steroid dependent, aspirin intolerant or evidence of Chlamydia pnuemoniae infection). There was a positive effect on symptoms (Standardised Mean Difference -1.25, 95% Confidence Intervals (CI) -1.80, -0.70) and markers of eosinophilic inflammation; eg sputum eosinophils Weighted Mean difference -78.5, 95%CI -90.8, -66.1). Tests of oral corticosteroid-sparing effects have not yet been performed on the newer agents such as roxithromycin and clarithromycin. REVIEWER'S CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗
PubMed2002

Clinical use of Levofloxacin in the long-term treatment of drug resistant tuberculosis.

Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. IN VITRO ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.

Adult↗
PubMed2001

Major histocompatibility locus genetic markers of beryllium sensitization and disease.

Hypersensitivity to beryllium (Be) is found in 1-16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only approximately 50% of BeLPT-positive workers present with lung granulomas (i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-alpha polymorphism TNF-alpha-308 in 23 individuals presenting as "sensitized" (i.e. BeLPT-positive without lung granulomas) and in 22 presenting as "diseased" (i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with "disease" (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4-10.0), whilst the high TNF-alpha production-related TNF-alpha-308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2-19.1) with no difference between "sensitization" and "disease". Furthermore, the HLA-DRArg74 marker was associated with "sensitization" without disease (OR 3.96, p=0.005, 95%, CI 1.5-10.1). The data indicate that tumour necrosis factor-alpha, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.

Adult↗
PubMed2001

First report of the Italian register for diffuse infiltrative lung disorders (RIPID).

RIPID was established in 1998 as a joint project of the major Italian scientific societies for Respiratory Medicine, with the aim to create an Italian Register on diffuse infiltrative lung disorders that can provide the basis for epidemiological and clinical studies of adequate sample size. In the period from May 1998 to December 2000, 1,382 cases were submitted from 54 Centers in 15 regions of Italy, 54.2% males (mean age +/- SD 50.5 +/- 16.8 years) and 45.8% females (50.2 +/- 15.3 years). A current smoking habit emerges in 18% of subjects; former smokers and never-smokers represent 26% and 56% of the total case series, respectively. The most frequent disease registered is idiopathic pulmonary fibrosis (37.6%), followed in decreasing order by sarcoidosis (29.2%), and Langherans' cell hystiocytosis (6.6%). High resolution computed tomography (HRCT) was considered as the most important tool for final diagnosis in the majority of cases (74.4%); 39.4% of patients underwent transbronchial biopsies, 39.2% bronchoalveolar lavage (BAL). A surgical biopsy was performed in 20.5% of patients. A web site has been activated from December 2000 (www.pneumonet.it/ripid), allowing prompt access to all information and scientific material concerning the project and to an electronic form for data collection that can be completed on-line.

Adult↗