A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis.

BACKGROUND: Cyclooxygenase-2, a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E2, is downregulated in lung tissue from patients with idiopathic pulmonary fibrosis. OBJECTIVE: To investigate the association between COX2.3050 (G --> C), COX2.8473 (C --> T) and COX2.926 (G --> C) single nucleotide polymorphisms (SNP) and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. DESIGN: Genetic polymorphisms were analyzed in 121 out of 225 available control subjects and in all of 174 patients with idiopathic pulmonary fibrosis by real time polymerase chain reaction. Logistic regression analysis of covariance and chi-squares test were used for statistical analysis. RESULTS: While analysis of disease development did not find any significant association with single SNP genotype, a haplotype analysis revealed a strong association between the disease development and one haplotype [GC] at loci COX2.3050 and COX2.8473, and suggested a recessive genetic effect of this haplotype. Further analysis concluded that subjects having two copies of [GC] haplotype, or equivalently (GG/CC) genotype at the two SNPs, had an increased risk after adjusting for age and sex. Due to the interaction, this elevated risk increased slowly with age, and the estimated odds ratio (OR) decreased with age from OR = 1.4 at age 30 to OR = 1 at age 74 and OR = 0.96 at age SO. The OR was significantly greater than 1 up to age 66, and not significant for age older than 66. Therefore, the recessive effect of [GC] haplotype increased the risk of IPF of subjects younger than 66 years, but its effect diminished for seniors older than 66. One hundred and forty-nine patients with idiopathic pulmonary fibrosis were followed up for 33.7 +/- 2.1 months. Further analysis of disease progressions, defined by the changes in pulmonary function tests, did not reveal any association with either SNP genotypes or haplotypes. CONCLUSIONS: The carriage of double homozygote (GG/CC) at the SNP loci of COX2.3050 and COX2.8473 polymorphisms may increase the susceptibility to idiopathic pulmonary fibrosis, by approximately 1.4 folds at age 30 and by a smaller fold greater than 1 up to age 66 years, but not the progression of the disease. These findings may help to improve our understanding of idiopathic pulmonary fibrosis pathogenesis and may lead to the development of new therapeutic strategies.

Severe and recurrent episodes of bronchiolitis obliterans organising pneumonia associated with indolent CD4+ CD8+ T-cell leukaemia.

The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.

Spontaneous pneumothorax and pneumomediastinum in IPF.

Patients with idiopathic pulmonary fibrosis (IPF) are at risk for a variety of acute pulmonary complications, including pneumothorax and pneumomediastinum. Our aim was to describe the radiographic and CT findings and to determine the frequency of complicating spontaneous pneumothorax and pneumomediastinum in patients with IPF. A retrospective study was performed including 78 consecutive patients who underwent CT scanning of the chest and who had confirmed IPF. The chest radiographs and CT scans were reviewed by two chest radiologists and classified as showing features of extra-alveolar air collections. The CT scans showed extra-alveolar air in 9 (11.2 %) of 78 patients (six females and three males; age range 26-90 years, mean age 65 years). Pneumothorax was demonstrated in 5 patients and mediastinal air collections in 4 patients. All patients had dyspnea for 1-48 months (mean 14 months). Of the five cases with pneumothorax, four developed acute onset of dyspnea and pleuritic chest pain, whereas 1 patient had a relatively stable functional status. Of the 4 patients with pneumomediastinum, three presented with nonpleuritic chest pain and acute dyspnea. Chest radiographs showed extra-alveolar air in 6 patients. Three cases were predicted to be negative by chest radiographs. Follow-up CT showed that air collections had resolved completely in 5 patients. Two patients died of respiratory failure within 4 months after CT. Extra-alveolar air should be recognized as a relatively common IPF-related complication. Chest CT is a useful imaging method in determining air collections in patients with IPF that become acutely breathless and their chest radiograph fails to reveal the presence of extra-alveolar air.

Subcutaneous sarcoidosis associated with vitiligo, pernicious anaemia and autoimmune thyroiditis.

We report a patient with pernicious anaemia, primary autoimmune hypothyroidism and vitiligo, who presented with subcutaneous nodules. Histopathology of the nodules revealed noncaseating granulomas, consistent with a diagnosis of sarcoidosis. Mild pulmonary sarcoid was also detected. Although an association between sarcoidosis and other autoimmune diseases is well-recognized, the presence of the particular autoimmune diseases in our patient and the involvement of subcutaneous fat in the sarcoidal inflammation, appears to represent a most unusual clinicopathological combination.

Mediastinal lymphadenopathy in cryptogenic fibrosing alveolitis: the effect of steroid therapy on the prevalence of nodal enlargement.

PURPOSE: To determine the prevalence of enlarged mediastinal lymph nodes in cryptogenic fibrosing alveolitis (CFA) and to assess whether this frequency was related to steroid administration. MATERIAL AND METHODS: Retrospective review of chest radiographs and high-resolution computed tomography (CT) of 54 patients with proven cryptogenic fibrosing alveolitis (CFA). Twenty-two of the 54 patients received oral steroids up to 2 months before the time of high-resolution CT examination (group 1); the remaining 32 patients had not taken steroids for at least 6 months before study entry (group 2). The prevalence, distribution, and size of enlarged mediastinal lymph nodes was determined in all groups. The diagnosis of CFA was histologically established in 44 patients. In 10 patients the diagnosis of CFA was based on clinical and high-resolution CT findings. RESULTS: Mediastinal lymphadenopathy was present in 26 of 54 patients with CFA. The prevalence of enlarged nodes was 14% (three of 22) in patients who had received oral steroids up to 2 months before the time of CT examination, and 71% (23 of 32) in patients that had not taken steroids for at least 6 months before study entry. CONCLUSION: We conclude that patients with CFA on steroid therapy had a significantly lower prevalence of mediastinal adenopathy (P < 0.001) than patients who had not taken steroids.

The crazy-paving pattern in exogenous lipoid pneumonia: CT-pathologic correlation.

OBJECTIVE: The purpose of our study was to show a distinctive appearance of exogenous lipoid pneumonia on thin-section CT that has not, to our knowledge, been previously documented. CONCLUSION: On thin-section CT, exogenous lipoid pneumonia is revealed as patchy well-defined areas of ground-glass attenuation with superimposed septal thickening (crazy-paving pattern). Exogenous lipoid pneumonia should be included in the differential diagnosis when thin-section CT reveals a crazy-paving pattern.

Febarbamate-induced pulmonary eosinophilia: a case report.

Subacute pulmonary hypersensitivity to febarbamate is reported, manifested by peripheral eosinophilia, skin rash and pulmonary bilateral infiltrates. Bronchoalveolar lavage showed an increased eosinophil count, and transbronchial biopsy an intraalveolar and interstitial eosinophil infiltration. The reaction cleared on cessation of the drug, and a rechallenge test with febarbamate induced peripheral eosinophilia and skin rash.