Gold pneumonitis. A case report with electronmicroscopy and electron probe analysis

A case of classical RA developed severe interstitial pulmonary disease and respiratory failure while on chrysotherapy. A high concentration of gold was found in lung tissue. Electron microscopic and electron probe examinations confirmed the presence of gold in the interstitial and intra-alveolar macrophages. The clinical course and possible pathogenic mechanism were discussed.     

Bronchoalveolar lavage fluid evaluation in rheumatoid arthritis

Rheumatoid arthritis (RA), a systemic disorder of unknown cause, is associated with a variety of well-recognized pulmonary abnormalities including interstitial lung disease. To investigate possible pathogenic events in this disorder, we performed bronchoalveolar lavage (BAL) in 24 patients with classic or definite RA. Using radiographic and physiologic parameters as well as BAL cell differentials, 3 distinct groups emerged. Group I consisted of 9 patients with evidence of clinical interstitial lung involvement. Group II consisted of 5 patients without evidence of clinical interstitial lung disease (normal chest roentgenogram and functional testing) but who had abnormal BAL cellular differentials. The 10 remaining patients (Group III) had no evidence of clinical interstitial lung disease and had normal BAL cell differentials. Bronchoalveolar lavage in Group I had a significantly increased percentage of neutrophils (12.4 +/- 4.2; p less than 0.05) compared with Group II (2.4 +/- 0.8) and Group III (2.9 +/- 0.6). All patients in Group II had elevated BAL lymphocytes (24.4 +/- 6.4) compared with Group I (10.1 +/- 3.8; p greater than 0.05) and Group III (5.4 +/- 0.7; p less than 0.01). Both Groups I and II had detectable IgM in BAL (0.02 +/- 0.01 and 0.04 +/- 0.02 mg/mg of albumin, respectively), whereas Group III patients and normal control subjects did not (p less than 0.01). There was a marked reduction in BAL T-lymphocyte Leu 3/Leu 2A (helper/suppressor) cell ratios in Group I (0.92 +/- 0.02; p less than 0.05) compared with Group II (2.6 +/- 0.6) and Group III (1.6 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease

Up to 80% of patients with scleroderma have lung disease, with interstitial lung disease (ILD) being the most common manifestation. Currently, there is no definitive therapy for this condition. The objective of the study is to investigate the use of mycophenolate mofetil (MMF) to treat scleroderma interstitial ILD. We report a retrospective chart review of 17 patients with scleroderma ILD treated with MMF (2g/day) for at least 12 months. Demographics, bronchoalveolar lavage (BAL) findings, pulmonary physiology and high-resolution computed tomography were recorded at baseline and after 12 and 24 months of therapy. Baseline BAL (n=12) showed alveolitis (median of 18% neutrophils). Ninety-four percent of subjects had either improved or stable lung function after 12 months of treatment: four improved, 12 were stable and only one worsened. All patients had radiographic abnormalities consistent with ILD. After 12 months of therapy, radiological findings (n=15) were stable in 11 patients, worse in three, and improved in one. There were no side effects attributable to MMF therapy recorded. Treatment of patients with scleroderma ILD for up to 24 months with MMF was generally associated with stable pulmonary function. These data argue for a prospective trial using MMF to treat scleroderma ILD.     

Subclinical alveolar inflammation in rheumatoid arthritis: superoxide anion, neutrophil chemotactic activity and fibronectin generation by alveolar macrophages

Interstitial lung disease (ILD) can be detected by pulmonary function testing (PFT) in 30-40% of rheumatoid arthritis (RA) patients. We assessed by bronchoalveolar lavage (BAL) the patterns of alveolitis in 21 RA patients: group 1 comprised 12 patients without evidence of ILD, and group 29 patients with clinical ILD defined by abnormal pulmonary function tests and/or chest X-ray. Cellular characteristics of BAL were studied in both groups. In addition, alveolar macrophages (AM) from patients in group 1 were isolated, and three parameters of cellular activation were studied: superoxide anion, fibronectin and neutrophil chemotactic activity generation. Total cell counts were not increased in group 1 but significantly increased in group 2 compared to controls. In group 1, 5/12 patients had elevated lymphocyte percentage (greater than 18%) suggesting subclinical lymphocyte alveolitis. In contrast, neutrophil alveolitis (greater than 4%) was found in 7/9 patients in group 2, mean percentage 12.9 +/- 4.2, compared with 1.2 +/- 6.4% in controls and 1.9 +/- 0.5% in group 1. These changes were not correlated with disease duration nor rheumatoid factor titres. Marked elevation of lymphocyte percentage was observed in patients with abnormal serum beta-2-microglobulin. Alveolar macrophages from group 1 patients released increased amounts of superoxide anion (7260 +/- 2700 vs controls 850 +/- 120 URL/5.10(5) cells), neutrophil chemotactic activity (21 +/- 4.8 vs controls 8.1 +/- 0.7 cells/HPF), and fibronectin (6.1 +/- 1.6 vs controls 1.3 +/- 0.2 ng.10(6) cells/hour). Whether or not lymphocyte alveolitis and/or AM dysfunction are pathogenic mechanisms of subsequent interstitial lung disease in patients who are still free of symptoms remains to be determined.     

Bronchoalveolar lavage (BAL) in newly diagnosed patients with collagen vascular diseases

Collagen vascular diseases (CVD) are commonly associated with interstitial lung diseases. Bronchoalveolar lavage (BAL) fluid analysis has important diagnostic value when considered in conjunction with other information. The present study was undertaken in newly diagnosed patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) at presentation to characterise BAL cellular constituents and elucidate the cellular picture in patients with and without pulmonary symptoms and in those with and without radiological (high resolution computed tomography) features of interstitial lung disease. All the patients were non-smokers and had not received any form of treatment for their diseases. The means of percentages of lymphocytes, neutrophils, and macrophages were 23.3%, 6.2%, 70.5% respectively. There was a significant BAL lymphocyte predominance in patients with pulmonary symptoms, and a lymphocyte and neutrophil predominance in those having radiological evidence of interstitial lung disease.     

Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled study

OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with rheumatoid arthritis (RA) who had previously discontinued infliximab treatment. METHODS: 24 patients with RA who discontinued treatment with infliximab (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously) for 12 months. The results were compared with those for 25 patients with RA receiving adalimumab who had not previously used an anti-tumour necrosis factor alpha inhibitor (controls). Disease activity was measured with the 28 joint count Disease Activity Score (DAS28), and clinical response with the American College of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no differences in demographic, clinical, and laboratory features between the two groups. After 12 months' adalimumab treatment, clinical improvement was similar in both groups. More specifically, ACR 20% response criteria were achieved by 18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four switchers discontinued the study-two because of adverse events and two because of lack of efficacy, while three control patients discontinued the study-one because of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a well tolerated and effective treatment for patients with RA, even when infliximab has been discontinued.     

Fibrinopeptide A reactive peptides and procoagulant activity in bronchoalveolar lavage: relationship to rheumatoid interstitial lung disease

Extravascular, primarily, alveolar fibrin deposition is commonly associated with the alveolitis of many interstitial lung diseases including the interstitial lung disease associated with rheumatoid arthritis (RA). We therefore hypothesized that coagulation pathways, which promote fibrin formation, would be activated in the alveolar lining fluids of patients with rheumatoid interstitial lung disease. To test this hypothesis, we studied the bronchoalveolar lavage (BAL) fluids from patients with rheumatoid interstitial lung disease (n = 7) and patients with RA unassociated with interstitial lung disease (n = 10) to characterize and quantitatively compare the BAL procoagulant material and levels of fibrinopeptide A (FPA), which is cleaved from fibrinogen by thrombin. FPA reactive peptide concentrations were significantly greater in rheumatoid interstitial lung disease than RA when normalized per ml of concentrated BAL fluid (p = 0.02), per mg BAL total protein (p = 0.01) or BAL albumin content (p = 0.03) and correlated with BAL antigenic neutrophil elastase concentrations (r = 0.87). Procoagulant activity was present in similar concentration of BAL of patients with RA and rheumatoid interstitial lung disease and was mainly attributable to tissue factor associated with factor VII (or VIIa). Our results demonstrate that tissue factor and factor VII are endogenous in the alveoli of subjects with RA and interstitial lung disease and could interact with distal coagulation substrates which may enter the alveoli in interstitial lung disease to locally promote fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ocular chrysiasis correlated with gold concentrations in the crystalline lens during chrysotherapy

The eyes of 11 patients with rheumatoid arthritis (RA) who received extended chrysotherapy (mean cumulative dose greater than 7 grams during a mean 6-year period) were examined biomicroscopically. Minute reddish-purple particles were seen in the cornea (corneal chrysiasis) in 5 and in the lens (lens chrysiasis) in 4 patients. Particulate deposits were absent in 11 other RA patients who had not received gold treatment. Seven crystalline lenses from 5 gold-treated patients were removed surgically because of incidental cataract formation and analyzed for gold content using neutron activation analysis. Although the mean lens gold concentration was higher in these patients than in non–gold-treated controls without RA (0.0073 m̈g/grams versus 0.001 m̈g/grams), the absolute gold level was markedly lower than that found in 25 diverse tissues analyzed previously. This finding is compatible with the absence of clinical gold-related lens disease or visual impairment.     

Induced sputum as a tool for early detection of airway inflammation in connective diseases-related lung involvement

BACKGROUND: Induced sputum (IS) sampling is a safe and validated approach to study bronchial inflammation in chronic obstructive lung diseases. Although promising results have also been reported in various diffuse interstitial lung disorders, the potential use of IS in the assessment of connective tissue diseases (CTD)-related lung involvement has not yet been investigated. AIM OF THE STUDY: To evaluate the clinical usefulness of IS in the early management of patients suffering from rheumatoid arthritis (RA) and systemic sclerosis (SSc) at the onset of respiratory symptoms. PATIENTS AND METHODS: The study population included 19 patients (RA=12; SSc=7) and 14 age- and sex-matched healthy volunteers. Lung function testing, high resolution computed tomography (HRCT) of the thorax and IS collection were performed in all cases. Broncho-alveolar lavage (BAL) was obtained in selected patients. RESULTS: IS samples from patients contained a significantly higher percentage of neutrophils and a lower percentage of macrophages compared to healthy subjects (p=0.002 and 0.001, respectively), while the total cell number showed no differences. In addition, sputa yielded both higher cell counts and higher neutrophils than BAL samples (p=0.02 in all instances). No correlations were found between IS findings and lung function parameters, HRCT and BAL findings. CONCLUSIONS: This is the first study investigating the inflammatory cell pattern in IS from CTD patients with early clinical evidence of lung involvement. Future studies are needed to determine whether the assessment of airway inflammation adds significant information that may result in a relevant improvement of disease management.     

Selective concentration and localization of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients.

Gold distribution was studied in the tissues of 7 rheumatoid patients who had died from 0 to 23 years after stopping chrysotherapy (sodium aurothiomalate) and in 23 samples of synovial tissue removed surgically at intervals during chrysotherapy in 5 patients. After the application of a highly specific staining technique, the cellular localization of gold was examined microscopically in various tissues: the amounts of gold in selected areas of the same specimens which had been examined microscopically were then measured by neutron activation analysis. During active chrysotherapy gold was abundant in synovial lining cells except where a fibrin layer was present on the surface; after stopping chrysotherapy, gold disappeared from the synovial lining cells. Gold accumulated progressively in the subsynovial connective tissues during chrysotherapy, but was not uniformly distributed, and bore no relationship to fluctuations in serum gold levels. Gold deposition was not confined to joint tissue, but was found within the macrophages of many organs, renal tubular epithelium, and, after recent chrysotherapy, in seminiferous tubules, hepatocytes, and adrenal cortical cells. Gold persisted in synovial and other tissues for up to 23 years after chrysotherapy was stopped. The overall findings indicated that gold is selectively concentrated within inflamed synovial tissues during chrysotherapy.     

Broncho-alveolar lavage in pulmonary involvement in rheumatoid arthritis

This study was designed to investigate by bronchoalveolar lavage (BAL) the characteristics of lung involvement in rheumatoid arthritis (RA). Twenty six patients with RA were included; ten were active smokers. Chest X Ray, pulmonary function tests and BAL were performed in all patients. Bronchiolitis was found in 7% of cases, pleurisy in 30% of cases. 83% of patients were found to have diffuse alveolar and/or interstitial disease, 17% rheumatoid nodules. Functional evaluation showed a restrictive pattern and a significant reduction in the carbon monoxyde diffusing capacity. Smokers had elevated BAL macrophages and decreased lymphocytes compared with non-smokers: respectively 89% vs 62.9% and 7.3% vs 18.9%. Patients with bronchiolitis had lower FVC than others: 38 +/- 14% vs 61 +/- 3%, and their BAL neutrophils were increased: 71 +/- 23% vs 7.5 +/- 2%. There was an inverse correlation between neutrophil counts and FVC in non-smokers, and diffusing capacity. We conclude that BAL inflammatory cells profiles are abnormal in RA and modified by a smoking history and the existence of a bronchiolitis.     

Bronchoalveolar lavage in systemic sclerosis with lung involvement: role and correlations with functional, radiological and scintigraphic parameters

To evaluate the role and the prognostic value of bronchoalveolar lavage (BAL) in scleroderma patients with interstitial lung disease. We reviewed the records of 79 patients with systemic sclerosis (SSc) who had dyspnea and pulmonary involvement and underwent BAL study. Sixty-two patients were prospectively followed up for 12–36 months and re-evaluated by pulmonary function tests (PFTs). Seventy-nine SSc patients were enrolled (71 F and 8 M), 55 with limited and 24 with a diffuse form; mean age 55 ± 13 years; mean disease duration 55.2 ± 59 months. All patients were ANA positive, of these 30 were anti-topoisomerase-1 positive (anti-Topo1) and 22 were anti-centromere positive (ACA). Thirty-one patients had alveolitis (39.2%) that was neutrophilic in 12 patients, eosinophilic in 3 and mixed (neutrophilic and eosinophilic) in 16 patients. Compared to patients without alveolitis, those with alveolitis had a significant reduction of carbon monoxide diffusing capacity (DLCO), forced vital capacity (FVC) and more elevated lung high-resolution computed tomography (HRCT) scores. Furthermore, alveolar clearance was significantly accelerated. No differences were found between patients with and without alveolitis regarding disease subsets (diffuse vs limited-SSc); a significant predominance of anti-Topo1 antibodies was found in the alveolitis group and of ACA antibodies in the non-alveolitis cohort. During the follow-up, (range: 12–36 months) 62 patients, 26 with and 36 without alveolitis were re-evaluated with PFTs. In the alveolitis group, 12 patients (46.1%) showed stable lung function parameters and 14 had worsened (53.8%). In this group, 20 patients (77%) received cyclophosphamide (CYC): 11 (55%) worsened (5 of them died of cardio-pulmonary complications) and 9 (45%) remained stable. Six patients could not be treated; of these 3 remained stable and 3 worsened. Among 36 patients with normal BAL, 11 (30.5%) showed stable lung function parameters, 13 improved (36.1%) and 12 worsened (33.3%); in this last group, 2 patients died of extra-pulmonary complications. Six patients, with progression of lung fibrosis, were treated with CYC: 3 of them improved and 3 remained stable. Our study revealed a trend toward a more severe course in the SSc patients with BAL alveolitis; probably the non-significant result is related to the low number of the examined subjects and to the selection criteria. However, BAL remains the only tool to exclude lung infections and, in our experience, a useful instrument to evaluate interstitial lung disease in SSc patients.     

Gold therapy in women planning pregnancy: outcomes in one center

OBJECTIVE: To review the experience and outcome of pregnancies in women taking gold while planning pregnancy. METHODS: We undertook a chart review of patients attending for gold injection and monitoring between January 1992 and April 2006. For women who became pregnant while being followed taking gold therapy, we extracted demographic, treatment, and disease activity data, information regarding pregnancy complications, outcome, and postpartum course. For details missing from the clinic records, patients were interviewed by the clinic nurse. RESULTS: Fourteen women experienced 20 pregnancies while being followed in the gold monitoring clinic. Mean age at the time of conception was 34.5 years (range 24-41), disease duration 8.5 years (1-16). Rheumatoid factor was positive in 9 of 14 women. Duration taking gold prior to conception was < 12 months in 7 pregnancies, 13-24 months in 4, 25-34 months in 2, and 2-10 years in 7 pregnancies. Four women continued taking gold until delivery. The rest of the women discontinued gold when they knew they were pregnant, with the exception of one who held her gold 4 weeks prior to conception. There were 5 spontaneous abortions in the first trimester; included were 2 spontaneous abortions in a woman with known Robertsonian chromosomal translocation. Sixteen babies were healthy including a pair of twins. One baby was born with weakness of one extraocular muscle requiring surgery; one had blocked tear ducts at birth. Rheumatoid arthritis (RA) flared during 3/15 completed pregnancies and postpartum and post-spontaneous abortion in 18/20 pregnancies. CONCLUSION: Our clinic experience and the published literature support the current practice that in patients with RA, gold may still be considered a treatment option in women planning pregnancy.     

Prognostic implications of bronchoalveolar lavage neutrophilia in patients with Pneumocystis carinii pneumonia and AIDS

The clinical records and bronchoalveolar lavage (BAL) cell differential counts were analyzed in 96 patients at risk for Pneumocystis carinii pneumonia (PCP) from human immunodeficiency virus (HIV) infection to determine if this information may be prognostically useful and to identify possible mechanisms of BAL neutrophilia. In 60 patients with PCP, 15 fatalities or episodes of respiratory failure occurred, and 14 of these patients had greater than 5% BAL neutrophils. Only one of 33 patients with PCP and less than 5% BAL neutrophils died. In contrast, there was no correlation between survival and BAL neutrophil percentages in 33 patients who did not have PCP. Three patients with HIV infection without lung disease had normal BAL cell differentials. Intra-alveolar and interstitial leukocytes found in 17 transbronchial lung biopsies in patients with PCP indicate that the alveolar and interstitial compartments of the lung may be the source of BAL neutrophils. Pathologic evidence of increased severity of diffuse alveolar damage to explain BAL neutrophilia was not found. As BAL neutrophil percentages in PCP had both positive and negative predictive value, this information may be useful to stratify therapeutic trials or to identify the patient with PCP who is at high risk of a complicated or fatal outcome.     

Bronchoalveolar lavage in children with chronic diffuse parenchymal lung disease.

The aim of the present study was to compare cellular and noncellular components of bronchoalveolar lavage fluid (BAL) in a group of children with a diagnosis of chronic diffuse parenchymal lung disease (cDPLD) and a group of children without parenchymal lung disease undergoing BAL for various clinical indications (control group). We evaluated cellular and non-cellular components (total proteins, albumin, hyaluronic acid, and fibronectin) in BAL fluid from 14 children (7 boys and 7 girls; mean age 9.2 years, range 5 months to 18.4 years) fulfilling the clinical and radiological diagnosis of chronic cDPLD, and in 19 controls without evidence of lung disease. The 14 patients were assigned to two study groups: early-stage cDPLD (6 patients; age range 5 months to 5.2 years; duration of illness, 5-7 months) and long-standing cDPLD (8 patients; age range 9.6-18.4 years; duration of illness, 1.2-17.6 years). Ninety-three percent of the patients with cDPLD had at least two BAL constituents outside normal limits, with high numbers of cells, including all types of alveolar cells, but especially lymphocytes and foamy macrophages. These findings indicate a mixed, predominantly lymphocytic alveolitis. Our patients also had a significant increase in two noncellular BAL components, namely fibronectin and hyaluronic acid. BAL samples from children with long-standing cDPLD contained increased numbers of lymphocytes, whereas samples from children with early-stage cDPLD contained increased percentages and numbers of foamy macrophages and increased concentrations of fibronectin, hyaluronic acid, and albumin. In conclusion, we clearly identified an abnormal BAL profile in our group of cDPLD patients. Moreover, BAL findings differentiated younger cDPLD patients in the early stages of their illness from old patients with long-standing disease.     

Increased alveolar plasminogen activator in early asbestosis

Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of gold-reactive T lymphocytes in rheumatoid arthritis patients treated with gold.

OBJECTIVE. To assess the role of T lymphocyte sensitization in the etiology of side effects of gold therapy in patients with rheumatoid arthritis (RA). METHODS. Lymphocyte proliferation induced by gold(III) and gold(I) salts was measured in 53 subjects: 30 RA patients with gold-induced side effects (17 with dermatitis, 9 with proteinuria, 3 with hematologic complications, and 1 with colitis), 9 RA patients without side effects despite prolonged chrysotherapy, 4 RA patients who had never received gold, and 10 healthy controls. Peripheral blood lymphocytes were cultured with the different gold salts and proliferation was measured by 3H-thymidine incorporation. RESULTS. Thirteen of the 17 RA patients who developed gold-induced dermatitis showed significant T lymphocyte proliferation in response to gold(III) salts, and this proliferation could be completely blocked by monoclonal antibodies directed at the HLA-DR molecule. Such proliferative responses were not seen in patients with other gold-induced side effects, in patients who had never received gold, or in healthy controls. Only 1 of 9 patients who had not developed side effects despite long-term maintenance chrysotherapy showed significant lymphocyte activation with gold(III) salts. Lymphocyte proliferation could not be induced with gold(I) salts or with other metal salts. CONCLUSION. Patients with RA who develop dermatitis following treatment with sodium aurothiomalate [gold(I)] have T cells which proliferate in an HLA-DR-restricted manner in response to HAuCl4 [gold(III)]. We believe this observation can lead to more accurate diagnosis and treatment of side effects, which currently limit the use of one of the most effective antirheumatic drugs.     

间质性肺疾病支气管肺泡灌洗前后肺功能及血气的改变

目的探讨支气管-肺泡灌洗(BAL)对肺生理功能的影响.方法对42例间质性肺疾病(实验组)灌洗前和灌洗后进行肺功能和动脉血气检测,并与7例无肺疾病非吸烟者做对照(对照组).结果实验组肺活量占预计值百分比(VC%)由灌洗前的(74±17)%,下降到灌洗后(64±19)%.一秒钟用力呼气容积占预计值百分比(FEV1%)由(72±9)%下降到(65±12)%.动脉血氧分压(PaO2)由(77±11)mmHg下降到(63±11)mmHg.对照组灌洗后上述指标虽有所下降,但统计学分析差异无显著性.结论BAL对间质性肺疾病患者的肺功能和动脉血气有一定影响.     

Cellular and noncellular components of bronchoalveolar lavage fluid in HIV-1-infected children with radiological evidence of interstitial lung damage

Children with acquired immune deficiency syndrome (AIDS) commonly have recurrent infectious and noninfectious lung complications that ultimately end in death. To study the intensity of alveolar inflammation and to evaluate the clinical utility of bronchoalveolar lavage (BAL) in children with HIV-1 infections, we retrospectively analyzed differential cell counts, lymphocyte subsets, and fibronectin and hyaluronic acid concentrations in BAL fluid of 18 HIV-1-positive children (9 boys, mean age 3.5 years, range 5 months-8 years) with radiological evidence of interstitial lung disease, and 19 control children who had undergone BAL for clinical indications not involving the lung parenchyma (13 boys, mean age 3 years, range 2 months-14 years). BAL fluid from 89% of the HIV-1 infected children showed CD8+ve lymphocytic alveolitis expressing HLA-DR, CD54, and CD 69 antigens. BAL fluid from HIV-infected patients typically contained markedly increased percentages and numbers of lymphocytes (P < 0.0001) and eosinophils (P < 0.04) and significantly higher concentrations of albumin (P < 0.05) and fibronectin (P < 0.0006) than fluids from control children. Whereas BAL cellular components did not differ in P. carinii-positive and P. carinii-negative HIV-1-infected children, fibronectin concentrations were significantly higher in P. carinii-positive than negative children. BAL cell differentials and noncellular components were related neither to severity of disease nor to patients' disease progression. These findings indicate that BAL is useful in studying the intensity of lung inflammation in children with HIV-1 infections and radiologically documented interstitial lung disease, but provides no information on the subsequent clinical course.     

The Differing Patterns of Subclinical Pulmonary Involvement in Connective Tissue Diseases as Shown by Application of Factor Analysis

To explore common patterns of interstitial lung disease (ILD) in symptomless patients with connective tissue disease (CTD), we applied factorial analysis to determine the relationship among the factors. A selected cohort of 71 non-smoking patients with a confirmed diagnosis of CTD [24 with primary Sjo¨gren’s syndrome (pSS), 21 with systemic sclerosis (SS), 20 with rheumatoid arthritis (RA) and six with polymyositis/dermatomyositis (PM/DM)] were identified. The diagnostic techniques included pulmonary function tests, bronchoalveolar lavage (BAL), chest radiographs and high-resolution computed tomography (HRCT). Disease extent and severity were assessed by a radiological and HRCT grading system. Three factors, accounting for 67% of the total variance, were extracted. The first factor (disease duration, diffusing lung capacity, neutrophils and CD8+ T cells on BAL, radiographic score and HRCT reticular score), with the highest percentage of variance (36.5%), defines a fibrotic lung pattern. The second factor (17.9% of variance) identifies an inflammatory lung pattern (macrophages, lymphocytes and eosinophils on BAL and HRCT ground-glass score). The third factor (12.6% of variance) represents a ventilatory function pattern (forced vital capacity, total lung capacity and forced respiratory volume in 1 s). The negative correlation between the fibrotic lung pattern and ventilatory function pattern, but not with the inflammatory lung pattern, suggests the presence of a significant derangement of the alveolar structures. In conclusion, application of factor analysis reveals various lung disease patterns in patients with CTD that might have different prognostic implications. Received: 2 March 1999 / Accepted: 9 July 1999