Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND: The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS: We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS: In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION: This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

[Bronchoalveolar lavage findings in patients with diffuse interstitial lung disease: prospective study of a cohort of 562 patients]. / Hallazgos en el lavado broncoalveolar de pacientes con enfermedad pulmonar intersticial difusa. Estudio de una cohorte prospectiva de 562 pacientes.

OBJECTIVE: Study of the bronchoalveolar lavage (BAL) fluid in some interstitial lung diseases can reveal patterns typical to each disease and that can support the diagnosis. The objective of this study was to perform a descriptive analysis of the cytologic study and of the lymphocyte subpopulations in BAL fluid from patients with interstitial lung disease. MATERIAL AND METHODS: In this prospective, observational study of 562 patients between January 1991 and January 2005, BAL fluid was analyzed to determine the distribution of cell populations and of lymphocyte subsets: CD3, CD4, CD8, CD3(+)CD4(-)CD8(-), and CD56. RESULTS: The mean age was 53.4 years and 53.3% of the patients were women. The following diseases were studied: idiopathic pulmonary fibrosis (n=132), sarcoidosis (n=123), connective tissue diseases (n=133), cryptogenic organizing pneumonia (n=89), and extrinsic allergic alveolitis (n=85). Isolated lymphocytic alveolitis was common in sarcoidosis and extrinsic allergic alveolitis. Mixed alveolitis was the most common pattern in the other interstitial lung diseases. The CD4:CD8 ratio was the most useful parameter. It was high in sarcoidosis (median, 2.3); the ratio was low or inverted in the other interstitial lung diseases, with median values of 1.76 in idiopathic pulmonary fibrosis, 0.45 in extrinsic allergic alveolitis, 0.35 in cryptogenic organizing pneumonia, and 0.33 in the connective tissue diseases. CONCLUSIONS: BAL parameters, in association with clinical and radiologic data, help to discriminate between interstitial lung diseases. BAL should therefore be considered a very useful tool in clinical management, particularly when pulmonary biopsy is not conclusive or is not possible.

[Response to inhaled granulocyte-macrophage colony-stimulating factor in a patient with alveolar proteinosis]. / Proteinosis alveolar. Respuesta al tratamiento con factor estimulante de colonias de granulocitos y macrófagos por vía inhalada.

Pulmonary alveolar proteinosis is a rare disease characterized by the accumulation of lipoproteinaceous material derived from alveolar surfactant in the alveoli, with a consequent deterioration in gas exchange. Pathogenesis is related to impaired phagocytic function of alveolar macrophages. In recent years, a new treatment for pulmonary alveolar proteinosis-consisting of subcutaneous administration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-has become available. The commonly accepted treatment, and the one to have shown greatest efficacy in pulmonary alveolar proteinosis, is whole lung lavage. Instead of subcutaneous administration, GM-CSF can also be inhaled as an aerosol. This route of administration of GM-CSF is safe and effective in the treatment of pulmonary alveolar proteinosis and represents an alternative to subcutaneous administration or whole lung lavage. We present a patient with pulmonary alveolar proteinosis who was treated with inhaled GM-CSF and describe her clinical and functional outcome after 1 year of treatment.

Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure.

BACKGROUND: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease. PATIENTS: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA. RESULTS: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM. CONCLUSIONS: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure.

[Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease: data from the Spanish patient registry]. / Neumonía intersticial descamativa y bronquiolitis respiratoria asociada a enfermedad pulmonar intersticial: datos del registro español.

Among the idiopathic interstitial lung diseases, respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and desquamative interstitial pneumonia (DIP) make up a subgroup of rare diseases that are clearly smoking related. Few large case series have been published. We describe 19 cases registered in Spain: 12 patients with DIP and 7 with RB-ILD. Clinical and radiologic features are described along with clinical course, treatments applied, and outcomes. With the exception of 2 patients with DIP, all were smokers or ex-smokers. Cough and dyspnea were the most common symptoms at onset in both diseases. The most frequent radiologic findings were ground-glass opacity in DIP and pulmonary nodules in BR-ILD. Most patients were treated with corticosteroids. Outcomes were good in general; only 1 patient, with DIP, died.

High-dose acetylcysteine in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO)). RESULTS: A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03). CONCLUSIONS: Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.

Incidence of interstitial lung diseases in the south of Spain 1998-2000: the RENIA study.

UNLABELLED: This study aims to describe the distribution of interstitial lung diseases (ILD) in the South of Spain. METHODS: A prospective multicentre population-based registry was established in nine provinces in the south of Spain with a population of 6,848,243 during a 3-year period (1998-2000). The number of participant physicians was 36 among 29 public hospitals. The number of diagnoses recorded was 66, divided in eight categories and coded according to ICD-9. A consensus document was elaborated for the classification of diseases and their diagnostic criteria. The number of cases declared was analysed each 3 months and communicated to each one of the participants. RESULTS: There were 744 cases of them registered with an annual incidence of 3.62 cases/ 100,000. 40.1% of diagnoses were biopsy confirmed. Men had a slightly higher incidence (4.18 cases/ 100,000/year) than women (3.07 cases/100,000/year). The most frequent diseases found were: idiopathic interstitial pneumonias (38.58%), ILD associated to systemic diseases (20.97%), and Sarcoidosis (11.69%). According to province distribution, most of the cases were grouped in an area between the provinces of Seville and Cordoba, which comprised more than 50% of cases. CONCLUSIONS: The study of the incidence of ILD depicts an intermediate situation from previous studies on the incidence and distribution of this group of diseases.