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Luca Richeldi

Publications and source records attributed to Luca Richeldi.

18 recordsLinked to original sources
PubMed2026

Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.

RATIONALE: Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES: To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS: We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS: We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS: We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

Aged↗
PubMed2007

T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis infection.

Young children exposed to tuberculosis have a high risk of progression to severe tuberculosis disease, but diagnosis of recent infection is hindered by the poor sensitivity of the tuberculin skin test. Whether new blood tests can detect latent infection in this vulnerable group is unknown because there is no gold standard. We monitored a tuberculin skin test-negative infant whose mother had infectious multidrug-resistant tuberculosis with enzyme-linked immunospot, a blood test that enumerates Mycobacterium tuberculosis-specific T cells. The enzyme-linked immunospot test became persistently positive by 6 months, and 18 months later the child developed active tuberculosis despite appropriate chemoprophylaxis. At this point, the magnitude of the enzyme-linked immunospot response increased >10-fold. Our findings demonstrate that this blood test detected latent infection with dormant, yet viable, bacilli and illustrate how enzyme-linked immunospot could improve diagnosis of childhood tuberculosis infection.

Antigens, Bacterial↗
PubMed2006

Impact of a T cell-based blood test for tuberculosis infection on clinical decision-making in routine practice.

New T cell-based blood tests for tuberculosis infection could improve diagnosis of tuberculosis but their clinical utility remains unknown. We describe the role of the ELISpot test in the diagnostic work-up of 13 patients presenting with suspected tuberculosis in routine practice. Of the seven patients with a final diagnosis of active tuberculosis, all were positive by ELISpot including three with false-negative tuberculin skin test results. Rapid determination of tuberculosis infection by ELISpot accelerated the diagnosis of tuberculosis, enabling early treatment initiation.

Aged↗
PubMed2006

Room size is the major determinant for tuberculin conversion in health care workers exposed to a multidrug-resistant tuberculosis patient.

OBJECTIVE: Transmission of Mycobacterium tuberculosis (MTB) to health care workers (HCWs) still represents a public health concern. A total of 71 obstetric workers underwent contact tracing after recent workplace exposure to a highly infectious multidrug-resistant tuberculosis patient [i.e., index case (IC)]. Aim of the study was to identify the main exposure predictors for the risk of conversion through evaluation of tuberculin screening results. METHODS: HCWs were investigated by a questionnaire (community, occupational, IC exposure risk factors) and tuberculin skin test screening. RESULTS: Conversion was detected in 5 (8%) of the 63 exposed workers and was not associated with either community or previous work-related risk factors. According to risk assessment, tuberculin conversion was related to neither amount time of exposure, workshifts, nor number of contacts. Conversely, an exposure to the IC in different hospital rooms was found significantly different among converters compared to non-converters (chi (2), P = 0.004). In particular, conversion was associated with exposure in two (obstetric emergency room, ambulatory discharge) out of the nine contact environments. Tuberculin conversion rates were associated with the room cubations of the exposure environments (chi (2) for trend, P < 0.01) and with worker age. In a logistic regression model adjusted for age, the lower room cubation was found the strongest predictor for tuberculin conversion (OR = 2.46, P = 0.02). CONCLUSION: The study shows that the factors affecting airborne mycobacterial dose (patient infectiousness, low sized confined rooms) were the major determinants for MTB transmission after a brief exposure to a highly infectious TB case.

Adult↗
PubMed2006

An update on the diagnosis of tuberculosis infection.

Targeted testing and treatment of individuals with latent tuberculosis infection at increased risk of progression to active disease is a key element of tuberculosis control. This strategy is limited by the poor specificity of the tuberculin skin test in populations vaccinated with bacille Calmette-Guérin and its low sensitivity in immunosuppressed persons, who are at highest risk of progression. Two blood tests (T-SPOT.TB and QuantiFERON-TB Gold), based on detection of IFN-gamma released by T cells in response to M. tuberculosis-specific antigens, may offer an improvement on the skin test. However, validation is challenging due to the lack of a diagnostic gold standard. This critical appraisal of published evidence summarizes the diagnostic accuracy of the new tests. The blood tests have operational advantages over the skin test because no return visit is required, results are available by the next day, and repeated testing does not cause boosting. Both tests are significantly more specific than the skin test in populations vaccinated with bacille Calmette-Guérin. The data suggest that T-SPOT.TB may be more sensitive than the skin test. Data in groups at high risk of progression to disease are scarce, and more research is needed in these populations, but it is clear that T-SPOT.TB performs better than the skin test in young children and HIV-infected people with active tuberculosis. Incorporation of these tests into programs for targeted testing of latent tuberculosis infection will reduce false-positive and false-negative results inherent in tuberculin testing, equipping clinicians with more accurate tools for tuberculosis control and elimination in the 21st century.

Antigens, Bacterial↗
PubMed2006

Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study.

BACKGROUND: Two commercial blood assays for the diagnosis of latent tuberculosis infection--T-SPOT.TB and QuantiFERON-TB Gold--have been separately compared with the tuberculin skin test. Our aim was to compare the efficacy of all three tests in the same population sample. METHODS: We did a prospective study in 393 consecutively enrolled patients who were tested simultaneously with T-SPOT.TB and QuantiFERON-TB Gold because of suspected latent or active tuberculosis. 318 patients also had results available for a tuberculin skin test. FINDINGS: Overall agreement with the skin test was similar (T-SPOT.TB kappa=0.508, QuantiFERON-TB Gold kappa=0.460), but fewer BCG-vaccinated individuals were identified as positive by the two blood assays than by the tuberculin skin test (p=0.003 for T-SPOT.TB and p<0.0001 for QuantiFERON-TB Gold). Indeterminate results were significantly more frequent with QuantiFERON-TB Gold (11%, 43 of 383) than with T-SPOT.TB (3%, 12 of 383; p<0.0001) and were associated with immunosuppressive treatments for both tests. Age younger than 5 years was significantly associated with indeterminate results with QuantiFERON-TB Gold (p=0.003), but not with T-SPOT.TB. Overall, T-SPOT.TB produced significantly more positive results (38%, n=144, vs 26%, n=100, with QuantiFERON-TB Gold; p<0.0001), and close contacts of patients with active tuberculosis were more likely to be positive with T-SPOT.TB than with QuantiFERON-TB Gold (p=0.0010). INTERPRETATION: T-SPOT.TB and QuantiFERON-TB Gold have higher specificity than the tuberculin skin test. Rates of indeterminate and positive results, however, differ between the blood tests, suggesting that they might provide different results in routine clinical practice.

Aged, 80 and over↗
PubMed2006

[New tools for a better diagnosis of latent tuberculosis infection].

Two new blood tests are today available for diagnosing latent tuberculosis infection. Both tests are based on the release of interferon-gamma from M. tuberculosis-specific T cells. These tests, QuantiFERON-TB Gold and T-SPOT.TB, are certainly more specific compared to the tuberculin skin test, and possibly more sensitive in some subgroups of patients; they might represent a crucial tool for tuberculosis control and elimination.

Humans↗
PubMed2005

Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection.

RATIONALE: Interferon (IFN)-gamma blood tests may improve the current level of diagnostic accuracy for tuberculosis infection. The QuantiFERON-TB Gold (QFT-Gold) has been used in selected populations and shows higher specificity than the tuberculin skin test (TST). OBJECTIVE: To evaluate the QFT-Gold test in unselected patients and assess the level of agreement with the TST. METHODS: The test has been routinely performed on whole blood samples in our microbiology laboratory for 8 months. Demographic, clinical, and microbiological data have been collected and correlated to the QFT-Gold results. MEASUREMENTS AND MAIN RESULTS: Of 318 patients tested, 68 (21.4%) gave an indeterminate (low positive mitogen control) QFT-Gold result. Indeterminate results were significantly overrepresented in patients with a negative TST (28.9% vs. 6.6% in TST-positive patients; p < 0.0001, chi2 test) and were more frequent in patients receiving immunosuppressive therapies than in those who were not receiving such treatments (odds ratio, 3.35; 95% confidence interval, 1.84-6.08; p < 0.0001). After excluding indeterminate results, the concordance between QFT-Gold and TST was significantly lower in Bacille Calmette-Guérin-vaccinated individuals (41.5%) than in nonvaccinated individuals (80.3%) (p < 0.0001). In 11 patients with active tuberculosis (5 culture-confirmed), QFT-Gold provided more positive results than the TST (66.7% vs. 33.3%; p = 0.165). CONCLUSIONS: The QFT-Gold test is feasible in routine hospital use for the diagnosis of tuberculosis infection. As with the TST, immunosuppression may negatively affect the test's performance, with a significant rate of indeterminate results in the most vulnerable population.

Adult↗
PubMed2005

Chronic beryllium disease: a model for pulmonary sarcoidosis?

Chronic beryllium disease (CBD) and pulmonary sarcoidosis are two distinct chronic disorders, sharing the pathological lung hallmark of the non-caseating granuloma and the immunological feature of T cell activation at the site of disease. However, while CBD is a rare occupational disease in which the cause, i.e. the inhalation of beryllium, is well known since a long time, the etiology of sarcoidosis, which is far more common in the general population, is still unknown. Since granuloma formation requires the presence of an immunogenic initiating antigen, it has been hypothesized that sarcoidosis is an antigen-triggered (auto)immune disease. Furthermore, while the study of large populations exposed to beryllium did made possible the identification of distinct genetic susceptibility factors in CBD, only recently the role of some genetic polymorphisms in sarcoidosis has been unraveled. Therefore, it seems likely that the advancement in the understanding of the immuno-pathogenesis of CBD will also help to design focused genetic studies to finally identify the etiology of sarcoidosis. Moreover, it is also possible that some cases of sarcoidosis are instead been caused by the inhalation of beryllium in genetically susceptible individuals.

Berylliosis↗
PubMed2005

The Italian register for diffuse infiltrative lung disorders (RIPID): a four-year report.

INTRODUCTION: RIPID (Italian register for diffuse infiltrative lung disorders) is a register aimed to create a national database of diffuse infiltrative lung disorders, also known as interstitial lung diseases. MATERIAL AND METHODS: The RIPID register collected prevalent data on patients affected by infiltrative diffuse lung disorders. The data form contains socio-demographic information (sex, age, years of education), existence in life, smoking habits, clinical data, diagnostic procedures (chest high resolution computed tomography (HRCT), bronchoalveolar lavage (BAL), transbronchial biopsies (TBB), surgical biopsies) and respiratory function tests at the time of diagnosis. RESULTS: Up to 18/01/2005 a total of 3152 patients had been included in the register. Seventy-nine centers and 138 physicians in all 20 regions of Italy contributed to patient enrolment. The vast majority of cases were from Northern Italy (2343 cases, 75%). The most frequently reported diagnoses were Sarcoidosis (1063 patients) and Idiopathic Pulmonary Fibrosis (IPF, 864 patients). DISCUSSION: The data in the RIPID confirm that epidemiological registries can be useful tools to investigate rare or relatively rare disorders (e.g. Sarcoidosis and IPF), in order to design multicentric clinical studies of adequate sample size, aimed at providing standardized diagnostic, management and follow up criteria with a particular regard to outcome.

Adult↗
PubMed2005

Steroid and/or other immunosuppressive therapies in idiopathic interstitial pneumonias: have they still a role?

The idiopathic interstitial pneumonias (IIPs) comprise a number of clinico-pathological entities of unknown origin, which are sufficiently different from one another to be designated as separate disease entities. The aim of this review is to describe the level of evidence available on the efficacy of corticosteroids and immunosuppressive, antifibrotic, or immunomodulatory therapies in the treatment of different IIPs.

Adrenal Cortex Hormones↗
PubMed2004

T cell-based tracking of multidrug resistant tuberculosis infection after brief exposure.

Molecular epidemiology indicates significant transmission of Mycobacterium tuberculosis after casual contact with infectious tuberculosis cases. We investigated M. tuberculosis transmission after brief exposure using a T cell-based assay, the enzyme-linked-immunospot (ELISPOT) for IFN-gamma. After childbirth, a mother was diagnosed with sputum smear-positive multidrug-resistant tuberculosis. Forty-one neonates and 47 adults were present during her admission on the maternity unit; 11 weeks later, all underwent tuberculin skin testing (TST) and ELISPOT. We correlated test results with markers of exposure to the index case. The participants, who were asymptomatic and predominantly had no prior tuberculosis exposure, had 6.05 hours mean exposure (range: 0-65 hours) to the index case. Seventeen individuals, including two newborns, were ELISPOT-positive, and ELISPOT results correlated significantly with three of four predefined measures of tuberculosis exposure. For each hour sharing room air with the index case, the odds of a positive ELISPOT result increased by 1.05 (95% CI: 1.02-1.09, p = 0.003). Only four adults were TST-positive and TST results did not correlate with exposure. Thus, ELISPOT, but not TST, suggested quite extensive nosocomial transmission of multidrug-resistant M. tuberculosis after brief exposure. These results help to explain the apparent importance of casual contact for tuberculosis transmission, and may have implications for prevention.

Adult↗
PubMed2004

Early diagnosis of subclinical multidrug-resistant tuberculosis.

BACKGROUND: Tuberculosis control hinges on prompt diagnosis of active cases and screening of contacts by tuberculin skin testing. Rapid blood tests for Mycobacterium tuberculosis infection are a new alternative to the tuberculin skin test, but whether they improve clinical outcomes is unknown. OBJECTIVE: To describe how a novel T-cell-based test for M. tuberculosis infection helped diagnose tuberculosis in an asymptomatic, immunosuppressed adult with a negative result on a tuberculin skin test. DESIGN: Case report. SETTING: Household contact. PATIENTS: Asymptomatic man receiving maintenance azathioprine therapy for Crohn disease whose wife had multidrug-resistant pulmonary tuberculosis. MEASUREMENTS: Enzyme-linked immunospot (ELISPOT) assay, computed tomography, and bronchoalveolar lavage cultures. RESULTS: The man had a negative tuberculin skin test result and a positive ELISPOT assay result. High-resolution computed tomography of the chest showed consolidation with early cavitation. Bronchoalveolar lavage and culture confirmed multidrug-resistant tuberculosis. LIMITATIONS: This single case report is a proof of concept and is not a formal evaluation of clinical utility. CONCLUSIONS: A positive ELISPOT assay result helped diagnose subclinical active tuberculosis in an immunosuppressed patient with a false-negative tuberculin skin test result. Large prospective studies that compare benefits and costs of this alternative to tuberculin skin testing are needed.

Adult↗
PubMed2003

MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients.

P-glycoprotein, a membrane-localized protein transporter, codified by the MDR1 gene, influences the response to pharmacological treatments, including antiretroviral drugs. MDR1 polymorphism C3435T is correlated with the functionality of the protein. We investigated the influence of this polymorphism in the reconstitution of the peripheral CD4 T cell pool in 149 drug-naive HIV-positive patients starting highly active antiretroviral therapy. The MDR1 C3435Tpolymorphism did not influence response to therapy, suggesting no disadvantages for individuals with a different genotype.

CD4 Lymphocyte Count↗
PubMed2003

Atypical lipomatous tumour (lipoma-like well-differentiated liposarcoma) arising in a pulmonary hamartoma and clinically presenting with pneumothorax.

We document an uncommon variant of pulmonary hamartoma (PH), discovered in the left upper lobe of a 60-year-old man after an episode of pneumothorax, a unique clinical presentation for such an occurrence. The tumour showed a prominent leaf-like pattern and was mainly composed of mature fat with adipocytes of different size and scattered throughout lipoblasts and floret-like cells. A lobectomy was performed and more than 7 years after surgery the patient's course is still uneventful. This case represents an exceedingly rare example of an histologically malignant change in PH and bears a close clinicopathologic resemblance to atypical lipomatous tumours of soft tissues.

Hamartoma↗
PubMed2002

Idiopathic pulmonary fibrosis: current and future treatment options.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology with an unfavorable outcome from progressively deteriorating respiratory function, leading ultimately to death from respiratory failure. It is characterized by sequential acute lung injury resulting in progressive fixed tissue fibrosis, architectural distortion and loss of function. An excess of profibrotic cytokines and/or a deficiency in antifibrotic cytokines have been implicated in the pathological process as has excessive oxidation. IPF is distinguished from other forms of diffuse pulmonary fibrosis by the presence of the specific histological pattern of usual interstitial pneumonitis. Oral corticosteroids are the usual treatment, but objective response rates are poor and good quality studies do not exist. Other therapies either alone or in combination with corticosteroids are widely used, including azathioprine, colchicine, cyclophosphamide and penicillamine. There is a paucity of good quality information regarding the effectiveness of most noncorticosteroid immunosuppressive agents. Older studies of lesser methodological quality have shown benefits from these drugs, generally when added to corticosteroids. Many were retrospective reviews or uncontrolled, nonrandomized, open-label, prospective studies and often included other histological patterns of disease which are now thought to respond better to immunosuppressive agents. The results of intervention with colchicine and azathioprine have been disappointing when assessed by good quality trials using modern diagnostic criteria. Modern high quality studies are lacking for several agents, notably cyclophosphamide and penicillamine. The older agents may yet prove to be effective but further good quality trials will be necessary to assess these agents adequately. Other new anti-inflammatory, antioxidant, antifibrotic or anticytokine compounds are largely untried or unreported. One trial using interferon-gamma-1b showed a significant improvement in pulmonary function but there are concerns regarding the generalizability of this study. Pirfenidone, cyclosporine and acetylcysteine may also prove to be of benefit but current studies are of insufficient quality to allow for any conclusions to be drawn. Currently there is no good evidence to support the routine use of oral corticosteroids, azathioprine, cyclophosphamide, penicillamine, colchicine, cyclosporine or any other immunosuppressive, antifibrotic or immunomodulatory agent in the management of IPF. Interferon, pirfenidone and other new agents may be of benefit but further studies are required. Any recommendations for treatment must therefore be made on an individual and empiric basis. As some other forms of pulmonary fibrosis may respond better to immunosuppressive agents, it remains important to make an accurate diagnosis, by open lung biopsy if necessary.

Adjuvants, Immunologic↗