HIV-related interstitial lung disease

The progressive breakdown of the cell-mediated immunity, which characterizes the natural history of HIV infection, invariably leads to the development of miscellaneous opportunistic infections or neoplasms involving a number of tissues, including the respiratory tract. In particular, given the extent and the severity of most infectious complications, it is not surprising that respiratory failure is a common finding in patients who have AIDS-related interstitial lung disease. Extensive knowledge of the sequence of events that starts with HIV infection of CD4+ cells and leads to the development of respiratory complications has been recently achieved. The present understanding of the pathogenesis of AIDS-related interstitial lung disease comes from the evaluation of cell populations retrieved from bronchoalveolar lavage fluid. In particular, the information gained from bronchoalveolar lavage studies led to the realization that HIV strains are present in the respiratory tract of HIV-seropositive subjects at all stages of infection. Furthermore, the characterization of bronchoalveolar lavage fluid cells proved to be central in evaluating the striking local immunologic reactions that can be detected in the lungs of these patients. Bronchoalveolar lavage studies have also demonstrated that local protective mechanisms may cause the shift toward accelerated progression to AIDS and the development of respiratory failure. This reviews briefly examines clinical aspects and cellular patterns of HIV infection in the respiratory tract. We will also consider data showing that HIV infection evokes an inflammatory response, initiated and sustained by cytotoxic T lymphocytes and macrophages and mediated by a number of cytokines that amplify host defenses as well as facilitate the spread of the retrovirus throughout the lower respiratory tract.     

Drug-induced interstitial lung disease

Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene into cultured myogenic cell lines from mouse and rat, and primary fetal human myoblasts. We also examined the effect of serum on liposome-mediated transfection and designed a new procedure to enhance transfection efficiency, based on the pre-condensation of plasmid DNA with polylysine. Polylysine pre-condensation was particularly effective when transfecting the cells in the presence of serum, a finding that could be significant for in vivo transfections.     

Clinico-pathological analysis of interstitial pneumonia associated with collagen vascular disease in patients with lung cancer

We investigated interstitial pneumonia associated with collagen vascular disease (IP-CVD) in association with lung cancer. Seventy-three cases of IP-CVD were included in this study. Nine (12%) of the 73 cases were associated with lung cancer, one of which had double lung cancers. The histological types of the cancers were adenocarcinoma (5 cases), epidermoid carcinoma (2 cases), small cell carcinoma, large cell carcinoma and large cell neuroendocrine carcinoma (one case each). The lesions were located in the central or peripheral lung in 3 and 7 of the ten cancers, respectively. Of the seven cases diagnosed as having IP-CVD followed by lung cancer, five had stage I disease, and one each of the remaining two cases was in stage IIIA and stage IV. Six of the seven peripheral cancer lesions which were resected or autopsied could be analyzed with regard to the topographical relationship between the primary site and fibrotic lesions. Only three cancers were encased by or in close proximity to, honeycomb lung, although most of the lung cancers arose in relation to fibrotic lesions. Moreover, the acute exacerbation of IP-CVD after operation or chemotherapy without thoracic irradiation should be monitored carefully.     

Thoracoscopic lung biopsy or open lung biopsy for interstitial lung disease

Both traditional open lung biopsy through a limited thoracotomy and VATS lung biopsy are effective methods for obtaining parenchymal samples in patients who have respiratory insufficiency and radiographic pulmonary infiltrates. For patients with slowly progressive disease processes, who require an elective biopsy, VATS biopsy is the procedure of choice because of the ability to visualize and sample multiple areas of the lung, and because of the decreased postoperative pain. On the other hand, when patients are critically ill and already on high-level ventilatory support, the VATS method offers no advantages over the standard minimal thoracotomy.     

Respiratory bronchiolitis-associated interstitial lung disease: a case report with bronchoalveolar lavage findings

We report a case of respiratory bronchiolitis-associated interstitial lung disease in a young asymptomatic heavy cigarette smoker. Diagnosis was achieved by examination of specimens obtained from open lung biopsy, but retrospective evaluation of bronchoalveolar lavage findings offer some circumstantial suggestions. We provide evidence for the nature of inclusions contained in alveolar macrophages. Problems related to the classification of respiratory bronchiolitis-associated interstitial lung disease are also discussed.     

Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease

Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistant to steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.     

Seropositive rheumatoid arthritis with interstitial lung disease in giant cell arteritis

Unusually high mortality rates have been recorded among HIV-infected tuberculosis patients in urban Africa 6 and 12 months after initiation of tuberculosis treatment--a trend that impedes efforts to achieve the 85% cure rate target set by the World Health Organization. This study investigated tuberculosis treatment outcomes in relation to HIV serostatus in a rural district of Malawi (Ntcheu). All 205 smear-positive pulmonary tuberculosis patients newly diagnosed in the district in 1995 received 2 months of daily supervised streptomycin, rifampicin, isoniazid, and pyrazinamide in the hospital followed by 6 months of isoniazid and thiacetazone at home. HIV testing, offered to all tuberculosis patients, was accepted by 110 (54%), 73 (66%) of whom were HIV-positive. By the end of treatment, 126 patients (61%) had been cured and 56 (27%) had died. Significantly fewer HIV-positive patients or patients who declined HIV testing were cured (59% and 55%, respectively) than those who agreed to testing and were HIV-negative (84%). The mortality rate was 29% among patients who tested HIV-positive, 8% among those with a negative test result, and 34% among patients who declined HIV testing. Acceptance of HIV testing improved over the course of the study period in response to changes in counseling techniques, especially clarification that blood taken for HIV testing would not be used for transfusions. Overall, these findings suggest that, in areas where HIV infection is prevalent, an 85% tuberculosis cure rate may be unrealistic.     

Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease

A sensitive protein-fold recognition procedure was developed on the basis of iterative database search using the PSI-BLAST program. A collection of 1193 position-dependent weight matrices that can be used as fold identifiers was produced. In the completely sequenced genomes, folds could be automatically identified for 20%-30% of the proteins, with 3%-6% more detectable by additional analysis of conserved motifs. The distribution of the most common folds is very similar in bacteria and archaea but distinct in eukaryotes. Within the bacteria, this distribution differs between parasitic and free-living species. In all analyzed genomes, the P-loop NTPases are the most abundant fold. In bacteria and archaea, the next most common folds are ferredoxin-like domains, TIM-barrels, and methyltransferases, whereas in eukaryotes, the second to fourth places belong to protein kinases, beta-propellers and TIM-barrels. The observed diversity of protein folds in different proteomes is approximately twice as high as it would be expected from a simple stochastic model describing a proteome as a finite sample from an infinite pool of proteins with an exponential distribution of the fold fractions. Distribution of the number of domains with different folds in one protein fits the geometric model, which is compatible with the evolution of multidomain proteins by random combination of domains. [Fold predictions for proteins from 14 proteomes are available on the World Wide Web at. The FIDs are available by anonymous ftp at the same location.]     

Eosinophilic lung disease associated with Candida albicans allergy

PURPOSE: We evaluate the effect of the provision of postgraduate educational material on improving practitioner knowledge base during a 3-year period. MATERIALS AND METHODS: A total of 210 urologists were provided 67 monographs in a 2-year period. They were given a pretest before and posttest 1 year after receipt of all monographs. RESULTS: There was significant improvement in posttest scores for the group as a whole. Improvement correlated with years post-training and number of monographs read. Multivariate analysis revealed the number of monographs read was the only independent predictor of outcome. CONCLUSIONS: Although the improvement in test scores was significant and did correlate with the postgraduate educational material read, it was modest. This finding raises significant concerns about the usefulness of this format for graduate medical education.     

Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease due to collagen vascular diseases

OBJECTIVE: Substantial toxicity limits the use of daily oral cyclophosphamide (CYC) for the treatment of interstitial lung disease (ILD) due to collagen vascular diseases. We examined whether intravenous (i.v.) pulse CYC can be substituted for daily oral therapy. METHODS: Six patients with rapidly progressive ILD due to polymyositis, systemic sclerosis, systemic lupus erythematosus, or primary Sj?gren's syndrome received 6-9 cycles of i.v. pulse CYC (0.5 gm/m2 of body surface area), together with an initial course of 50 mg of prednisolone, which was tapered to a maintenance dosage of 5-7.5 mg/day, and their response was measured clinically, by high-resolution computed tomography (HRCT) and by assessment of the bronchoalveolar lavage (BAL) cell profile. RESULTS: All patients showed significant improvement in exercise tolerance and lung function. Elevated BAL neutrophils dropped substantially, whereas the response of BAL lymphocytes was inconsistent. Low-attenuation opacities in the HRCT regressed in 4 patients and remained unchanged in 2, but reticular infiltrates remained largely unaffected. Remission was maintained with hydroxychloroquine, azathioprine, or cyclosporin A. CONCLUSION: I.v. pulse CYC proved to be an effective and well-tolerated treatment in these patients. Since it appears to target mainly the inflammatory component of the disease, it should be reserved for progressive ILD featuring indices of high inflammatory activity.     

Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset

Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin.     

Needle, transbronchial, thoracoscopic, or open lung biopsy in interstitial lung disease

The specific diagnosis of interstitial lung disease has conventionally been determined by lung biopsy. Lung biopsy also is useful for assessing disease activity and prognosis, and is sometimes useful in deciding on the necessity of therapy. The availability of newer biopsy techniques and the interaction of these techniques with current generation imaging modalities has changed the role of biopsy in interstitial lung disease. This review reports on the indications, techniques, and limitations of biopsy procedures and places them in the context of the use of current imaging methods, as reflected in recent literature.     

Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.     

Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease

Fourteen patients with systemic sclerosis (SSc, scleroderma) and interstitial lung disease were treated with oral cyclophosphamide (1-2 mg/kg/day) and low dose prednisone (< 10 mg/day). There was a significant improvement in FVC after 6 months compared to entry values (2.21 +/- 0.19 l vs. 2.03 +/- 0.15 l, p < 0.02). Improvement was maintained at 12 months (2.27 +/- 0.27 l, p < 0.05) and 18-24 months (2.60 +/- 0.28 l, p < 0.001). In 12 cases followed for 18-24 months, FVC was stable or improved. No significant improvement or decline was noted for the DLCO. Side effects included cytopenia (2), infection (1), and hemorrhagic cystitis (2), and one possible related malignancy. A controlled prospective trial of cyclophosphamide is warranted in patients with SSc and active interstitial lung disease.     

Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.     

Evidence of autoantibodies to cell membrane associated DNA (cultured lymphocytes): a new specific marker for rapid identification of systemic lupus erythematosus

OBJECTIVE: Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA. METHODS: Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes. RESULTS: This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sj?gren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible. CONCLUSION: This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.     

Fibromuscular dysplasia of the renal arteries associated with antiphospholipid autoantibodies: two case reports

A relationship appears to exist between antiphospholipid autoantibodies (APLA) and vascular occlusion, although the exact mechanism is still a matter of debate. We present and comment on two cases of renal artery occlusion in patients with concomitant presence of arterial fibromuscular dysplasia and high APLA titers.