Characteristics of medically and surgically treated empyema patients: a retrospective cohort study.

BACKGROUND: The role of drainage, intrapleural fibrinolytics, and/or surgery in the management of thoracic empyema is controversial. OBJECTIVES: We aimed to investigate the operational practice of empyema management at our hospital. METHODS: Between January 2001 and December 2008, all patients with thoracic empyema were retrieved. After exclusion of patients with malignant effusion, traumatic or iatrogenic empyema, and a history of pleurodesis or tuberculosis, we compared the characteristics of medically versus surgically treated empyema patients. RESULTS: Seventy-eight of 215 retrieved patients were acute bacterial empyema cases. All received intravenous antibiotics. Fifty-eight (74.4%) initially received tube thoracostomy, 34 (43.6%) were treated with intrapleural urokinase, and 30 (38.5%) were operated on. Of 20 patients without initial tube thoracostomy, 15 (75%) were operated on, compared to 9 (37.5%) who were initially treated by tube thoracostomy without intrapleural fibrinolytics (OR 5; 95% CI 1.4-18.5, p = 0.01) and 6 (17.7%) who were initially treated with tube thoracostomy and intrapleural urokinase (OR 14; 95% CI 3.6-53.6, p < 0.001). The surgery patients were not different in demographic and clinical characteristics but were more likely to describe significant chest pain 12 months after discharge. CONCLUSIONS: In this retrospective cohort study of thoracic empyema patients, initial chest tube insertion and intrapleural fibrinolytics were associated with less surgical therapy. Other predictors of the need for surgery could not be identified. Surgery patients were more likely to suffer from residual chest pain 12 months after discharge. Initial treatment with IV antibiotics, chest tube, and intrapleural fibrinolytics was successful in the majority of patients.

Acclimatization improves submaximal exercise economy at 5533 m.

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6-7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (W(max)) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6-7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max ) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6-7 (5533 m), VO(2) at 75% W(max) (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO(2) was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO(2) to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5-6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions.

Length of hospital stay for TB varies with comorbidity and hospital location.

BACKGROUND: Although most guidelines overwhelmingly recommend outpatient TB treatment, hospitalisations are common. We investigated the proportion of TB patients hospitalised and determined factors associated with length of stay (LOS) in Switzerland.METHODS: Cases with TB as the primary diagnosis were retrieved from a nation-wide hospitalisation database and compared to TB notifications. Month and year of admission, hospital site, type of TB, age, sex, LOS and up to 50 ICD-10 coded comorbidities were compared with controls matched for age, sex and admission date.RESULTS: From 2002 to 2015, the estimated TB hospitalisation rate was 81%. The median LOS of 6,234 TB patients was stable at 14 days (IQR 6-22), but increased in patients with miliary TB, old patients and with hospital location. TB-associated comorbidities included HIV, liver disease, anaemia, malnutrition and genitourinary tract diseases. LOS was associated with three comorbidity clusters: 1) malnutrition, cachexia and anaemia (median LOS 20 days, IQR 13-31); 2) toxic liver disease and hepatitis (median LOS 23 days, IQR 14-37.5); and 3) adverse drug events (median LOS 20 days, IQR 13-30).CONCLUSION: Most TB patients were hospitalised. LOS was related to TB type, comorbidities and hospital location. Promoting outpatient care is a priority to improve TB management in Switzerland.

Administrative monitoring of tuberculosis treatment in Switzerland.

SETTING: Treatment of tuberculosis (TB) is critically dependent on adherence. Directly observed treatment (DOT) has been shown to be effective. OBJECTIVE: To determine operational treatment outcome using administrative treatment monitoring (ATM) to assess the need for more vigorous promotion of DOT. DESIGN: Cohort study in eastern Switzerland, where ATM was started in 2002. Bi-monthly progress forms and a treatment outcome form (after 6 months) were sent to the treating doctors. Forms not returned within 6 weeks were followed up with phone calls. RESULTS: Between 2002 and 2004, 98 (87.5%) of 112 new TB patients completed a 6-month treatment course. Eight elderly patients died of causes other than TB while on treatment, four travelled out of the region and two were lost to follow-up. Treating doctors opted for DOT in only seven cases. CONCLUSION: Given the high success rate of 87.5% in our cohort, more vigorous promotion of DOT is not a priority for TB case management in eastern Switzerland. In our setting, ATM in collaboration with the family doctors offers a valuable alternative to the more time-consuming universal DOT.

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.

Extracorporeal photochemotherapy for Epstein-Barr virus-associated lymphoma after lung transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication after transplantation of solid organs. Highest incidence rates have been reported for lung transplant recipients. With the current treatment strategy for early onset PTLD, a reduction of immunosuppressive drugs, mortality of lung transplant recipients with PTLD remains high, due to both, incomplete control of PTLD and transplant rejection. We present a lung transplant recipient with a history of acute rejection and Epstein Barr virus-associated posttransplantation malignant non-Hodgkin's lymphoma. Extracorporeal photochemotherapy, in combination with a moderate reduction of immunosuppressive therapy, resulted in complete disappearance of PTLD. After a first year of follow-up, no further rejection and no recurrence of PTLD have occurred. Treatment with ECP, with its beneficial effects on both, rejection after organ transplantation and malignant lymphoma, may be a particularly valuable approach for the treatment of PTLD in patients after lung transplantation, with its increased risk for transplant rejection.

Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor.

BACKGROUND: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented. METHODS: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis. RESULTS: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found. CONCLUSION: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Periodic breathing during ascent to extreme altitude quantified by spectral analysis of the respiratory volume signal.

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores.

AIM: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. METHODS: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. RESULTS: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). CONCLUSIONS: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

[HIV-associated tuberculosis in Africa exemplified by Zimbabwe]. / HIV-assoziierte Tuberkulose in Afrika am Beispiel Zimbabwe.

In Africa, a rapid increase of human immunodeficiency virus (HIV)-associated tuberculosis cases has been observed; 80% of a worldwide 6 million dually infected persons live in this part of the world. The annual risk of progression to clinically overt tuberculosis in dually infected persons approaches the lifetime risk in persons with tuberculosis but no HIV infection. Zimbabwe is an example which illustrates the rapid increase in notified tuberculosis cases since 1985, accounted for primarily by HIV-associated tuberculosis cases. In sputum-smear positive HIV-associated tuberculosis, classical symptoms are reported with the same frequency as in HIV negative cases. Thus, case-finding activities need not be altered. In sputum-smear negative patients, reliable diagnostic tests are not available. Therapeutic trials are widely used and this causes overdiagnosis of tuberculosis. Extrapulmonary manifestations are common in HIV-associated tuberculosis. A majority of lymph node enlargements, pleurisy and pericarditis in Africa are now due to tuberculosis. If compliance is ensured, response to chemotherapy is excellent, but overall case fatality and relapse rates are increased. The cost-effectiveness of tuberculosis control programmes using directly observed therapy for at least the first 2 months of treatment is well established. With the prominent global significance of tuberculosis and the possibility of cost-effective interventions, a commitment to the fight against the worldwide epidemic is more important than ever before.

Characteristics of sputum smear-positive tuberculosis patients with and without HIV infection in a hospital in Zimbabwe.

Human immunodeficiency virus (HIV) infection has a large impact on tuberculosis in Africa. In this study, the prevalence of HIV infection in a population of hospitalized tuberculosis patients in Zimbabwe was determined and demographic characteristics, clinical signs and symptoms, as well as radiographic appearance were compared in tuberculosis patients with and without HIV infection. During a 5 month observation period, information on tuberculosis patients referred to Driefontein Tuberculosis Sanatorium, Mvuma, Zimbabwe was collected, computerized and analysed with commercially available software. Of 467 patients admitted, 255 were sputum smear positive for acid-fast bacilli. Of 196 patients with complete information, 127 (65%) were HIV-seropositive. When compared to the 69 HIV-seronegative patients, HIV-infected patients were not different in age, gender, the period of delay between the onset of symptoms and diagnosis, radiographic appearance, history of previous antituberculosis treatment and symptoms and signs reported, with the exception of herpes zoster and other sexually-transmitted disease. The prevalence of HIV infection in our population of tuberculosis patients was large. However, since demographic and clinical characteristics are remarkably similar in tuberculosis patients with and without HIV infection, case-finding activities need not be altered in the wake of the HIV epidemic.

PIP: During April-September 1992, demographic, clinical, and bacteriological information was collected on all 467 tuberculosis (TB) patients aged 15 years and older admitted to the Driefontein Tuberculosis Sanatorium serving people from the Midlands and Masvingo provinces in Zimbabwe. 255 people had at least one sputum smear positive for acid-fast bacilli. Researchers retained 196 of these for analysis and compared demographic characteristics, clinical signs and symptoms, and radiographic appearance in TB patients with and without HIV infection. 127 (65%) people tested positive for HIV. HIV-infected TB patients were not significantly different compared to HIV-negative TB patients in age, gender, the period of delay between the onset of symptoms and diagnosis (about 2 months for both groups), radiographic appearance, history of previous anti-TB treatment, and symptoms and signs reported. They were more likely than HIV-negative TB patients to have a history of sexually transmitted diseases (adjusted odds ratio = 3.4; p = 0.01) and herpes zoster infection (9 vs. 0 patients). These findings suggest that health workers need not change case finding activities in the wake of the HIV epidemic. In conclusion, the most cost-effective intervention continues to be identification and curative treatment of sputum smear-positive TB patients irrespective of their HIV status.

[Inhalational antibiotic therapy in patients with cystic fibrosis and Pseudomonas infection]. / Zur inhalativen Antibiotika-Therapie bei Patienten mit zystischer Fibrose und Pseudomonas-Befall.

Treating chronic Pseudomonas infection of the bronchial tree is a very important part of the treatment strategy in patients with cystic fibrosis. There are only a few antibiotics which are effective against pseudomonas. Many of them soon lead to bacterial resistance (e.g. fluoro-quinolones). Inhaling antibiotics produces high sputum concentrations and low systemic toxicity. Tolerance is good and resistance rare. Several clinical studies, some of them doubleblind placebo controlled, have shown a positive effect of inhaled antibiotics on symptoms, on frequency of necessary i.v. therapies and also on pulmonary function. Most commonly aminoglycosides (tobramycin) and colistin, which is not yet registered in Switzerland, are used. The main indication is chronic therapy of Pseudomonas infection.

Adverse reactions to peak flow monitoring. Report of 5 patients.

Five patients with adverse reactions to peak flow monitoring are presented: 2 patients had herniation of abdominal content, while the others presented with vasovagal syncope, minor depression and neurotic preoccupation with peak flow values, respectively. As a result, 3 of the 5 patients became noncompliant. For nonpsychological somatic adverse reactions, we calculated an incidence of 1.1 cases/1,000 patients started on peak flow monitoring. Adverse reactions with a psychological background may be more frequent. Clinicians should bear in mind that patients noncompliant with peak flow monitoring may have discontinued because of adverse reactions.

[Tuberculin testing of hospital personnel: large investment with little impact]. / Tuberkulin-Testung bei Spitalangestellten: grosser Aufwand mit geringem Nutzen.

Guidelines for the control and prevention of nosocomial tuberculosis include recommendations for surveillance of hospital employees with tuberculin skin tests (TST). We analysed a 2 1/2-year period of tuberculin skin testing at Kantonsspital St. Gallen, an 850-bed hospital in eastern Switzerland with 2000 employees and 21,000 admissions yearly. Tuberculosis cases among employees are reported for a 10-year period. TST were performed on engagement, if no recent positive result was available. A new TST was read in 717 (58%) of 1241 persons starting employment during the study period. In 261 workers in contact with 23 sputum smear positive tuberculosis patients, 180 (69%) follow-up TST were performed. Of a total of 37 increases in TST, 20 (54%) were retrospectively attributed to other causes than a recent infection with M. tuberculosis (vaccination with BCG, booster phenomenon, doubts concerning the previous test result). Of the remaining 17 TST converters, 5 finally completed a full course of preventive chemotherapy. With a total workload of 547 hours for this result, half a year's working hours were necessary to prevent one case of active tuberculosis. Over a 10-year period, 4 out of 9 active tuberculosis cases in employees were likely to be nosocomially acquired, but none was diagnosed thanks to TST surveillance. We conclude that surveillance with TST is time consuming, but has little impact on the tuberculosis situation in hospital employees. Alternative strategies to this unsatisfactory system are discussed.

False-positive Mycobacterium tuberculosis culture revealed by restriction fragment length polymorphism analysis.

BACKGROUND: The microbiological analysis of respiratory specimens is the most reliable approach to diagnose active pulmonary tuberculosis. PATIENT AND METHODS: We report a 60-year-old female patient (index patient) who underwent diagnostic bronchoscopy for chronic cough. No acid-fast bacilli were detected in bronchial washings. Although cough subsided with symptomatic treatment, Mycobacterium tuberculosis grew on egg-based media after 12 weeks. A false-positive culture result was suspected. Chart review and DNA fingerprinting were carried out. RESULTS: The bronchoscope used to examine the index patient was previously used for a 30-year-old patient (source patient) with smear- and culture-positive pulmonary tuberculosis. Restriction fragment length polymorphism (RFLP) analysis based on the IS 6110 element confirmed that the two strains were identical. CONCLUSION: Cross-contamination is a reason for false-positive cultures with M. tuberculosis and should be suspected in patients with a low clinical probability for active tuberculosis.

German version of the Epworth Sleepiness Scale.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is a questionnaire widely used in English speaking countries for assessment of subjective daytime sleepiness. OBJECTIVE: Our purpose was to translate and validate the ESS for use in German-speaking countries. METHODS: A German translation of the ESS was administered to 159 healthy German-speaking Swiss and to 174 patients with various sleep disorders. RESULTS: The mean +/- SD of ESS scores in normals was 5.7+/-3.0, in patients it was 13.0+/-5.1 (p<0.001). Scores were not correlated with age or gender but with the percentage of time spent at an oxygen saturation <90% (R = 0.35, p<0.001), and the respiratory disturbance index (R = 0.26, p<0.001) in primary snorers and sleep apnea patients. Item analysis confirmed internal consistency of the scale (Cronbach alpha = 0.60 in normals, and 0.83 in patients). Follow-up scores in 25 sleep apnea patients on treatment showed a reduction by 7+/-5 points (p<0.05). CONCLUSIONS: Our data validate the ESS for application in German-speaking populations. The simplicity, reliability and the apparent lack of relevant influences of language and cultural background on performance of the ESS makes it a valuable tool for clinical management and research.

Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies.

Interstitial lung disease (ILD) is a complication of polymyositis (PM) and dermatomyositis (DM). It often manifests itself in association with myositis-specific antisynthetase autoantibodies, among which anti-Jo-1 antibodies are the most commonly encountered. In contrast, ILD associated with anti-Jo-1 antibodies without muscle involvement is rare and not well characterized. We report four patients presenting with ILD associated with anti-Jo-1 antibodies. Histological findings of transbronchial biopsies disclosed a pattern consistent with nonspecific interstitial pneumonitis, a CD8+ lymphocytosis was found in bronchoalveolar lavage. Only one of these patients developed an "antisynthetase syndrome" with PM, after nearly 2 yrs of severe ILD. The clinical conditions of all four cases showed stabilization or improvement when cyclosporine was added to their immunosuppressive treatment. These cases confirm that a CD8+ lymphocytic interstitial lung disease may be the first, and sole manifestation of autoimmune disease associated with anti-Jo-1 antibodies. Furthermore, they suggest that this form of interstitial lung disease apparently has a poor response to steroids and cytotoxic drugs, but may respond to moderate doses of cyclosporine and azathioprine in addition to low doses of steroids.

BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF.

BACKGROUND: Idiopathic pulmonary alveolar proteinosis (PAP) has recently been recognised as a disease of impaired alveolar macrophage function caused by neutralising anti-granulocyte-macrophage colony-stimulating (anti-GM-CSF) autoantibodies. Subcutaneous recombinant human GM-CSF is a novel treatment for PAP, but its mechanism of action is unclear. METHODS: Clinical, functional, and bronchoalveolar lavage (BAL) findings were prospectively evaluated in a patient with PAP treated with daily subcutaneous GM-CSF 8 microg/kg for 12 weeks. RESULTS: Treatment resulted in improvements in dyspnoea, lung function, and peak cycle ergometry performance. In serum and BAL fluid the titre of anti-GM-CSF autoantibodies was raised at baseline and markedly reduced on treatment. At baseline the BAL fluid cellular profile showed a decrease in the absolute number and the percentage of macrophages (50%) and an increase in lymphocytes (45%), predominantly CD4+. This cellular distribution remained unchanged after 6 and 12 weeks of treatment while macrophages became morphologically normal and functionally improved. Extracellular proteinaceous material completely disappeared. CONCLUSIONS: Clinically successful treatment of PAP with GM-CSF was associated with a profound reduction in GM-CSF neutralising autoantibodies, improvement in alveolar macrophage morphology and function, but persistent BAL lymphocytosis.

Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis.

BACKGROUND: Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A - a]DO(2)), vital capacity (VC), and carbon monoxide transfer factor (TLCO), but alternative serological measures have been sought. Granulocyte-macrophage colony stimulating factor (GM-CSF) neutralising autoantibody is found in patients with idiopathic acquired AP. We have investigated the interrelationships between the levels of this antibody and those of surfactant protein (SP)-A and -B, lactate dehydrogenase (LDH), and conventional measures of disease severity, and the capacity of these parameters to predict the response to rhGM-CSF treatment. METHODS: Blood levels of anti-GM-CSF antibodies, SP-A, SP-B, LDH, and [A - a]DO(2), VC, and TLCO were measured before rhGM-CSF treatment and every 2 weeks thereafter in 14 patients with AP. RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83%. SP-A was highly correlated with [A - a]DO(2), VC, and TLCO (p