Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.

Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings.

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.

Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland.

BACKGROUND: The prevalence of sporadic and familial idiopathic pulmonary fibrosis (IPF) cases in Finland was evaluated according to the revised recommendations of the American Thoracic Society. METHODS: All Finnish pulmonary clinics (n=29) were included in the primary screening. Hospital data bases were used to identify patients with the diagnosis "alveolitis fibroticans idiopathica" (J84.1 in ICD-10 classification). The total number of patients with IPF was extrapolated based on the evaluation of random samples of case records in different centres. Families with more than one potentially affected member were identified from a questionnaire study and the diagnosis was verified from the medical records. RESULTS: Using this approach, the nationwide prevalence of IPF in Finland was estimated to be 16-18/100 000. In 90% of the patients lung involvement was assessed by high resolution computed tomographic (HRCT) scanning and in 31% a surgical biopsy specimen was available, further confirming the diagnosis. Seventeen multiplex families with 2-5 affected family members were identified, giving a prevalence of 5.9/million for familial IPF in Finland. Both multiplex and sporadic families were clustered in Eastern Finland. This clustering reflects the demographic history of Finland in the 16th century and suggests that multiplex families may share a common ancestor in the last 20-25 generations. CONCLUSION: The familial form explained 3.3-3.7% of all Finnish cases of IPF diagnosed according to the revised international guidelines. Geographical clustering of multiplex families suggests a recent founder effect in patients with familial IPF.

Zinc chloride smoke inhalation: a rare cause of severe acute respiratory distress syndrome.

Zinc chloride smoke inhalation is a rare cause of slowly progressive and often fatal acute respiratory distress syndrome (ARDS). The conventional treatment includes intravenous N-acetylcysteine, L-3, 4-dehydroproline, methylene blue, and respiratory support according to the lung protective strategy. This report presents the cases of three patients with serious zinc chloride inhalation and ARDS, the last of whom survived after prolonged intensive care, videothoracoscopic excision of emphysema bullae, and recurrent chemical pleurodesis.

Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis: a double-blind, placebo-controlled multicenter study. Finnish Pulmonary Sarcoidosis Study Group.

STUDY OBJECTIVE: To evaluate the efficacy of oral prednisolone, followed by inhaled budesonide, in patients with newly diagnosed (<3 months) stage I and stage II pulmonary sarcoidosis. DESIGN: Double-blind, placebo-controlled, parallel-group, multicenter study. SETTING: Twenty pulmonary medicine departments in Finland. PATIENTS: One hundred eighty-nine adult patients were randomized to treatment. Patients with erythema nodosum or stage IV sarcoidosis (pulmonary fibrosis), and patients requiring immediate treatment with oral corticosteroids for extrapulmonary lesions or chronic illnesses were excluded. TREATMENT: The patients received either oral prednisolone for 3 months (20 mg/d for 8 weeks, 15 mg/d for 2 weeks, and 10 mg/d for 2 weeks) followed by inhaled budesonide (Pulmicort Turbuhaler; Astra Draco; Lund, Sweden) for 15 months at 800 microg bid, or placebo tablets followed by placebo inhaler therapy. MEASUREMENTS: Chest radiographs, lung volumes (FVC), diffusing capacity of the lung for carbon monoxide (D(LCO)), serum angiotensin-converting enzyme (SACE), and beta2-microglobulin at 3-month intervals. RESULTS: After 3 months of treatment, radiographic improvements were seen in the active-treatment group when compared to the placebo-treatment group. At 6 months, the difference was still statistically significant. Later, no differences were found. In patients with initial stage I lesions, neither the FVC nor the D(LCO) (the percent predicted mean values) changed during the study, as they were normal from the beginning. In patients with initial stage II disease, the difference in the FVC mean values between the groups also remained unchanged throughout the study. In stage II patients treated for 18 months, but not earlier, the difference in D(LCO) became statistically significant; the largest differences were seen in patients with initial FVC values <80% of predicted and D(LCO) values <75% of predicted. The decrease in SACE in the active-treated stage II patients was significantly larger than in the placebo-treated patients. No difference was observed in adverse events between the active-treated patients and the placebo-treated patients. CONCLUSION: Treatment is not required for patients with stage I disease. An initial treatment with prednisolone followed by long-term inhalation of budesonide is more effective than placebo in patients with stage II disease. Sequential oral and inhaled corticosteroid therapy may be an alternative treatment regimen for stage II sarcoidosis patients, rather than long-term oral corticosteroid therapy alone.

A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo-controlled study.

BACKGROUND AND AIM: Oxis Turbuhaler is a new dry powder formulation of long-acting beta2-agonist formoterol. This study compared the efficacy and safety of regular use of the long-acting beta2-agonist formoterol and the short-acting terbutaline for 3 months in patients with asthma. METHOD: After 1-week run-in, 343 patients received either formoterol 12 microg bid (F) (delivered dose of 9 microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group, double-blind, randomized manner. They had a mean of 61% of predicted forced expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine percent used inhaled corticosteroids. RESULTS: During run-in mean morning peak expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P). The F group improved morning PEF significantly compared with P (P = .0022) and T (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P, respectively. The F group was statistically significantly better than P and T in increasing evening PEF and in reducing night-time asthma. The F and T statistically significantly reduced the use of rescue medication compared with P. The bronchodilating response to the study drug and to an additional 1.25 mg terbutaline was of the same magnitude before and throughout the study. No statistically significant treatment-by-time interaction was observed (P > .20). There were no adverse effects of clinical relevance. CONCLUSION: Formoterol Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg qid, and placebo. Regular use of formoterol or terbutaline did not significantly influence the response to additional inhalation of terbutaline.

Amplitude variation in static-charge-sensitive bed signal increased in obstructive airways disease.

The relationship between oesophageal pressure variation and amplitude variation in the static-charge-sensitive bed (SCSB) ballistocardiogram suggests that changes in intrathoracic pressure can be detected using the SCSB method. We investigated whether amplitude variation in the static-charge-sensitive bed ballistocardiogram (SAV) is related to severity of airway obstruction in patients with asthma and chronic obstructive pulmonary disease. The ability of SAV to detect an increase in airway obstruction induced by histamine challenge was also tested. Twenty-six patients suffering from asthma and 12 patients with chronic obstructive pulmonary disease (COPD) were enrolled in the study. SAV, amplitude from the SCSB ballistocardiogram, respiratory amplitude from the SCSB respiratory wave form and heart rate from the electrocardiogram (ECG) were computed using analysing software (Biorec, Helsinki, Finland) during a 7-min supine rest. SAV was related to forced expiratory volume in one second (FEV1) immediately after signal recording. Asthma patients participated in a standardized histamine challenge test to reveal the effect of acute bronchoconstriction on SAV. An inverse relationship existed between baseline FEV1 and SAV in asthma and COPD. In the histamine inhalation test, FEV1 fell by 0.7 +/- 0.3 l or 26% +/- 11% (P < 0.0001) and SAV increased by 12% +/- 5% (P < 0.0001) in 12 asthma patients. The fall in FEV1 induced by histamine followed regularly and correlated significantly with the rise in SAV (n = 24, r = -0.58, P = 0.002). Changes in respiratory amplitude or heart rate did not explain changes in SAV. SAV may not separate the upper airway obstruction from the bronchial obstruction but it is related to severity of airway obstruction. The clinically significant increase in airway obstruction induced by histamine inhalation increases amplitude variation in SCSB.

Ganciclovir prophylaxis after lung and heart-lung transplantation.

Cytomegalovirus (CMV) infection causes both acute and chronic allograft damage. The aim of this study was to analyze the utility of ganciclovir in preventing CMV infection in pulmonary allografts. Thirty five consecutive lung (LTX) and heart-lung (HLTX) transplant patients were studied from 1990 to 1996. CMV prophylaxis was started in January 1995. Recipients with CMV-positive serology received ganciclovir on postoperative days (POD) 7-28. Acyclovir was given on POD 29-90. Recipients with CMV-negative serology received ganciclovir on POD 7-90 if the serology of the donor was positive. CMV was demonstrated by rapid cell vial culture and/or detecting CMV-specific antigens in bronchoalveolar lavage (BAL) samples. The time point of the first BAL fluid specimen exhibiting CMV was estimated using the Life Table method. BAL samples of all the recipients without ganciclovir treatment became positive for CMV, whereas two of the 11 patients with ganciclovir administration remained negative. Ganciclovir significantly (P < 0.05) delayed but did not absolutely prevent CMV infection after LTX and HLTX.

En bloc heart and lung transplantation in Finland 1988-1996.

UNLABELLED: The purpose of the study was to review the first clinical experience in combined heart-lung transplantation in our institution. MATERIAL: From June 1988 to December 1996 15 en bloc heart and lung transplantations were performed. There were nine men and six women, aged 17-61 (mean 42.3) years. The indications for operation were primary pulmonary hypertension with right heart failure in five, Eisenmenger's syndrome in five, pulmonary embolism and right heart failure in three and emphysema with right heart failure in two cases. RESULTS: The hospital (30 day) mortality was four patients (26.6%). The causes of mortality were graft failure in two cases, infection and bleeding after transbronchial biopsy in one case and sepsis and aspergillosis in one case. Postoperative complications included eight cytomegalovirus (CMV), two Pneumocystis Carinii, five bacterial and five fungal (one Aspergillus and four Candida) infections. Rejection episodes (of the lungs) occurred in four patients (in 27%). During the follow-up to four years two patients developed diabetes mellitus (insulin therapy), one patient renal failure (dialysis), two patients tracheal stricture (laser resection), one patient fracture of the spine and one patient epilepsy. One patient died from prolonged CMV infection and chronic rejection eight months postoperatively. Four patients underwent bronchial artery revascularization (two with the internal thoracic artery and two with a vein graft). This was followed by improved airway healing and resistance towards infections. After a follow-up to four years 10 patients out of 15 (66.7%) were living an active life. CONCLUSION: Combined heart-lung transplantation offers a good mid-term outcome for patients with end-stage cardiopulmonary disease. The results compare favourably with the corresponding international statistics.

Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.

In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.

Immunodetection of Pneumocystis carinii in bronchoalveolar lavage specimens compared with methenamine silver stain.

Immunodetection of Pneumocystis carinii, based on immunofluorescence and use of a monoclonal antibody specific for an antigen located within the cyst wall and detectable after trypsin digestion only, was compared with a methenamine silver stain in 553 bronchoalveolar lavage specimens from immunosuppressed patients. P. carinii was found by immunofluorescence in 72 (86%) and by silver stain in 68 (81%) of the total of 84 positive samples detected by either or both of these methods.

Endothelin in bronchoalveolar lavage fluid is increased in lung-transplanted patients.

Animal studies have shown increased endothelin in bronchoalveolar lavage (BAL) fluid during unmodified rejection. We performed radioimmunoassay of endothelin in 59 BAL fluid samples from ten patients at different times after lung transplantation. All patients received immunosuppressive therapy (cyclosporin, azathioprine and methylprednisolone). Reference BAL samples were obtained from six controls. Of the 59 test samples, five were collected during rejection episodes, confirmed by clinical outcome, BAL cytology and radiology (rejection group), and 19 were taken during bacterial, viral or fungal infection (infection group). The endothelin content of BAL (pg/ml) was significantly greater in the rejection group than in the infection group (61.1 +/- 3.8 vs 40.6 +/- 2.0) or in the 35 samples taken in uncomplicated course after lung transplantation (40.9 +/- 5.4), p < 0.01. The endothelin level in BAL fluid from the controls was only 3.0 +/- 1.4 pg/ml, significantly less (p < 0.005) than in all the lung-transplanted groups. Endothelin in BAL fluid thus was increased after lung transplantation, and still further during rejection.

Nontuberculous mycobacterial infection in HIV-negative patients receiving immunosuppressive therapy.

The clinical significance of nontuberculous mycobacterial isolates and presentation of mycobacteriosis was compared in HIV-negative patients with or without preceding immunosuppression. Patients with nontuberculous mycobacterial isolates (n = 139), mainly from the respiratory system, were divided into three groups: those who had had previous immunosuppressive treatment (24%), those with other underlying diseases (54%) and those without predisposing factors (22%). The distribution of mycobacterial species among the various patient groups was similar. The immunosuppressed patients fulfilled the criteria of the American Thoracic Society for clinical mycobacteriosis less frequently (18%) than those with other underlying diseases (32%) or without predisposing factors (45%), p = 0.07, the difference being more striking for patients with Mycobacterium avium complex isolates. This was partly due to the difficulty in distinguishing the relevant symptoms from those caused by the underlying disease. The proportion of patients receiving antimycobacterial therapy differed similarly (18%, 21%, 45%, respectively). Among the immunosuppressed patients, positive acid-fast smears were significantly less common and polymicrobial infections, initial lymphocytopenia, fever and fatal outcome significantly more common. About half of the immunosuppressed patients died within one year. In order to better define patients requiring treatment, the criteria for localized mycobacteriosis among immunosuppressed patients should be reevaluated.

Asbestos bodies in bronchoalveolar lavage fluid in relation to occupational history.

Concentrations of asbestos bodies (AB) were assessed by optical microscopy of 10 ml iron-stained samples and compared with the exposure history acquired by personal interview for 156 patients. Concentrations equalling or exceeding 1 AB/ml were found in 85% of patients who had been heavily exposed to asbestos and only 7% of those who were unlikely to have been exposed. Elevated AB concentrations were observed among primary asbestos, shipyard and construction workers. Smoking was not found to affect the AB concentrations. The use of Papanicolaou-stained cytological Millipore preparations during routine screening was a less sensitive method for the assessment of AB concentrations than that involving iron-stained preparations. The expression of AB concentration as AB/ml or AB/million cells were found to be equally useful indicators of exposure. The correlation between AB concentration and exposure history was greater than in earlier studies on workers exposed to chrysotile. Concentrations exceeding 1 AB/ml were indicative of a nontrivial exposure to asbestos. Despite the observed correlation between AB concentration and exposure history, the individual variability of AB counts, methodological differences and laboratory-bound reference values are important in the interpretation of AB concentrations in bronchoalveolar lavage (BAL) fluid at individual level.