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There have been several recent reports of pulmonary disease resulting from exposure to Mycobacterium avium complex in indoor hot tubs. The disease is thought to be due either to infection or extrinsic allergic alveolitis (EAA). In this report we describe the case of a patient who developed episodes of fever, dyspnea and cough 4-6 hours after cleaning his indoor swimming pool. A diagnosis of EAA was made on finding a restrictive lung function pattern with gas exchange abnormalities, a predominant lymphocytosis in the bronchoalveolar lavage, diffuse ground-glass opacities in the lower lobes on high-resolution computer tomography, and specific IgG antibody activity to the swimming pool water. There was no precipitin reaction or specific IgG antibody activity to microbes extracted from the water. Interestingly, the water contained Mycobacterium avium complex (MAC) in huge amounts and in this case the histopathological features of the lung biopsy specimens differed from those seen in typical EAA, but were similar to those described in "hot tub lung" caused by mycobacteria. Solely by avoidance of cleaning the swimming pool, without any pharmacological treatment, the patient recovered completely within three months. To the best of our knowledge, this is the first report of EAA possibly associated with MAC exposure in a swimming pool environment.

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BACKGROUND AND OBJECTIVE: Recently an increasing number of patients presented with febrile and respiratory symptoms associated with exposure to a new type of domestic ultrasonic humidifier. PATIENTS AND METHODS: We report on 14 patients (5 females, 9 males; average age 42.5 17.4 years) with recurrent episodes of fever, cough and dyspnea after repeated exposure to ultrasonic misting fountain at home. RESULTS: A diagnosis of extrinsic allergic alveolitis (humidifier lung: 12 patients) or toxic alveolitis (humidifier fever: 2 patients) was made on the basis of the history and the clinical, radiological, laboratory and immunological findings. 10 patients had a partial respiratory insufficiency at rest or on exercise, 9 had a restrictive ventilatory abnormality. The chest x-ray was abnormal in 7 patients. Of 8 patients in whom computed tomography was done 6 had typical changes of an exogenous allergic alveolitis. Bronchoalveolar lavage revealed lymphocytic alveolitis in 8 patients. In 12 patients bacteria, moulds and/or yeasts were demonstrated in the humidifier fluid which they had used. 13 patients had IgG antibodies to the humidifier fluid. 8 patients were subjected to inhalative challenge tests to their own ultrasonic misting fountain: all of them had positive reactions. CONCLUSIONS: These cases demonstrate the potential of ultrasonic humidifying devices to cause illness in the home. In view of their increasing popularity, humidifier lung and humidifier fever should be considered in the differential diagnosis of patients with unexplained pulmonary or flu-like illness with fever.

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A 22-year-old woman developed recurrent episodes of fever, cough and dyspnea after repeated exposure to a misting fountain at home. A diagnosis of extrinsic allergic alveolitis (EAA) was made by detection of serum antibodies against the fountain water, by culture of Bacillus subtilis, Mucor racemosus, Mucor mucedo, and Saccharomyces cerevisiae from the water, and by detection of specific IgG antibodies against Bacillus subtilis and the Mucores. The diagnosis was confirmed by a restrictive lung function pattern, and a highly increased total cell count with a lymphocytosis of 39 % in the bronchoalveolar lavage. An inhalation challenge with the misting fountain resulted in a positive reaction. Because this humidifier system has recently become widespread at home, clinicians should be aware of this specific type of EAA which may be called "misting fountain alveolitis".

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Dendriform pulmonary ossification (DPO) represents a relatively frequent form of diffuse pulmonary and mostly clinically inapparent bone formation of unknown etiology. An association with other pulmonary diseases, particularly pulmonary interstitial fibrosis, has been suggested. Here we report a female patient with a 15-year history of DPO whereby at the age of 48 an X-ray of the thorax first revealed findings suggestive of pulmonary fibrosis. For 9 years the patient suffered from chronic progressive ventilation disorder and after a further 3 years open lung biopsy revealed DPO in conjunction with interstitial fibrosis. After a history of progressive respiratory failure the patient suddenly died of cardiac arrhythmia along with deteriorated cor pulmonale at the age of 71. Autopsy revealed an almost complete ossification of the lungs with an increasing gradient from apex to base. In contrast to previous reports, the DPO of our patient was life-limiting.

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A 52 year old farmer was referred to us for investigation of suspected farmer's lung. For many years the farmer had been exposed to hay, straw, pigeons, and fuel chip dust. Under exertion he suffered from shortness of breath. In the farmer's own fuel chips we could identify Aspergillus fumigatus, Paecilomyces species and Mucor species. In the farmer's blood we found IgG-antibodies against his own fuel chips, thermophilic actinomycetes, Penicillium species, Mucor species and Aspergillus fumigatus. We did not detect any IgG-antibodies against pigeon serum or pigeon faeces. In order to determine the responsible allergen we performed two challenge tests. In the first test the farmer had to inhale his own hay and straw dust for one hour. This provocation was negative. A second one-hour inhalative challenge was carried out 16 days later using his own fuel chips. This time he experienced significant pulmonary and systemic reactions: body temperature rose by 3.3 degrees C, leucocytes by 12,200/mm3; PO2 fell by 39.4 mmHg, vital capacity by 52%, DLCO by 36%. After the challenge the farmer complained of coughing and dyspnoea. Rales could be heard on auscultation, and an interstitial infiltrate was seen to develop on chest x-rays. After the challenge the patient had to be treated with oxygen and systemic corticosteroids. We diagnosed a fuel chip-induced exogenous allergic alveolitis (EAA). Eight days later the parameters were back to normal and the farmer was discharged from our hospital with further corticosteroid medication. This method of inhalative provocation is very important in diagnosing an EAA. Problems arise when the mode and duration of exposure to substances has to be chosen. Because of the risk of severe reactions, inhalative provocations relating to EAAs should only be performed in special centres with an intensive care unit. In this paper we present a diagnosis of fuel chip lung, which is rarely seen in Germany. However, with the rising use of fuel chips as heating material it is necessary to consider this use as a cause of EAA among farmers.

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To the authors' knowledge there have been no previous reports on the protection afforded by powered filtering respirators in farmers with occupational asthma attributed to the inhalation of organic dust. In order to investigate this question, 26 farmers with occupational asthma were challenged with an exposure to work-related dusts for up to 60 min. This resulted in highly significant increases in airway resistance (Raw), thoracic gas volume (TGV) and specific airway resistance (sRaw) compared to baseline values. After a mean period of 21 weeks the farmers were subjected to a second challenge, this time wearing a protective respiratory device (RD) with a P2 filter. Significant increases in Raw, TGV and sRaw were again observed, but on average these were 50-80% smaller than the increases seen when RDs were not worn. These differences were found to be statistically significant. This shows that the use of a respiratory device in farmers suffering from occupational asthma reduces the development of bronchial obstruction but does not prevent it. The use of this kind of respiratory device cannot substitute for the proper management of asthma since the devices do not offer complete protection.

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AIM OF THE STUDY: Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications. DESIGN: Group 1 received 4 brachytherapies with a dose of 3.8 Gy (at a 10-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a 10-mm depth) at a 3-week interval. At a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results. PATIENTS: Ninety-three patients with advanced cancer were included in the study; 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Karnofsky performance status, and histologic findings. INTERVENTIONS: A mean total irradiation dose of 13.4 +/- 5.2 Gy for group 1 and 13.7 +/- 4.4 for group 2 were applied (calculated at 10 mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth). RESULTS: The 1-year survival rate was 11.4% in group 1 and 20.4% in group 2. No significant difference in survival time was found, but mean survival was longer in group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was comparable in both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%). CONCLUSION: High-dose rate brachytherapy with 2 x 7.2 Gy with a 3-week interval is equivalent to a 4 x 3.8-Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.

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With the aid of provocative challenges with hay in patients suffering from farmer's lung, a comparison of the protective effectiveness of the Airstream Helmet (main filter P2) and of the Sundström Mask (main filter P3) was undertaken. A total of 42 farmers were admitted to the study. In 14, as indicated by an expertise, a workplace-related provocative challenge by the farmers' own hay was carried out and was shown to be positive with respect to the presence of farmer's lung disease. In 28 farmers in whom an inhalative provocative challenge with hay had been demonstrated to be positive, inhalative provocative challenges were again performed using the farmers' own hay while the farmers were wearing protective respirators--14 with the Airstream Helmet, (main filter P2) and 14 with the Sundström Mask (main filter P3). When the respirator was not worn, a statistically significant increase in the number of leukocytes and temperature vis-a-vis the baseline values was observed. Partial oxygen pressure, vital capacity, total lung capacity and DCO, all showed a statistically significant decrease as compared with the baseline figures. The provocative challenges performed while the subjects were wearing the respirators also revealed a statistically significant increase in the number of leukocytes and in temperature, which, however, was statistically significantly smaller than that induced by provocation without the respirator. A similar pattern of behaviour was also found in the decrease in vital capacity, oxygen partial pressure, total lung capacity and DCO. No statistically significant differences were observed between the provocation figures obtained with the Airstream Helmet as compared with those obtained with the Sundström Mask.(ABSTRACT TRUNCATED AT 250 WORDS)

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The results of a prospective follow-up study comprising 52 patients with central tumours of the lung submitted to endoluminal irradiation are reported. Additional external irradiation was possible in 30 patients (group A), but not in 22 patients (group B). Satisfactory immediate results were observed, together with a one-year survival rate of 39.3% (group A) and 12.5% (group B).

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Ten farmers with farmer's lung disease, and 15 healthy subjects who had not previously been exposed to hay, were exposed to hay for one hour. Over a period of twenty-four hours, the symptoms, number of leukocytes, temperature and pulmonary functional-analytical parameters were recorded. In all the cases with farmer's lung, and in seven of the healthy test subjects, broncho-alveolar lavages (BAL) were carried out prior to and 48 hours after the exposure to hay. In the patients with farmer's lung, a systemic, statistically significant reaction associated with an increase in the number of leukocytes to about 7,400/cmm, together with an increase in temperature of about 1.6 degrees C, occurred 8 hours after the initiation of the provocative test. In addition, a primary reaction developed, with a statistically significant decrease in vital capacity (VC) by 700 ml, of the total lung capacity (TLC) of 500 ml, and of the oxygen partial pressure of 14 mmHg. Four hours after the start of the provocation, the resistance increased, on average, by 0.5 cm H2O/l/s (p less than 0.05). In the case of the farmers with farmer's lung disease, a comparison of the cell composition of the BAL fluid prior to and after the provocative test revealed a decrease in the percentage of macrophages from 84.6 +/- 9.1% to 46.8 +/- 15.7% (p less than 0.003), an increase in the percentage of lymphocytes from 10.8 +/- 6.6% to 26.4 +/- 23.4% (p less than 0.04), and an increase in the percentage of polymorphs from 4.3 +/- 5.7% to 26.4 +/- 20.0% (p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

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14C-labeled azithromycin, a new macrolide antibiotic, was accumulated by various phagocytic cells isolated from volunteers or patients. The concentration of the antibiotic in monocytes, polymorphonuclear leucocytes (PMNLs), and alveolar macrophages was greater than that in the surrounding medium by a factor of between 200 and 668. Azithromycin penetrated somewhat more rapidly into PMNLs and monocytes than into alveolar macrophages. On the other hand the final concentration in the alveolar macrophages was greater by a factor of about 3 than that in the other two phagocytic cells. Staphylococcus aureus, Legionella pneumophila and Haemophilus influenzae previously taken up by the phagocytes were rapidly inactivated by low (0.031-0.5 micrograms/ml) concentrations of the antibiotic, which in the presence of the cells were subinhibitory. There is thus a clear synergism between azithromycin and the phagocytic cells which leads to increased intracellular killing of the bacteria.

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Six subjects with farmer's lung underwent double inhalation challenge tests, each lasting 60 min, using natural antigen exposure. Subjects underwent the tests first without and then with protection by a particle-filtering half mask. Our purpose was to determine whether and to what extent the use of such masks reduced or prevented symptoms in affected patients. Clinical assessment included general and pulmonary symptoms, HR, temperature, WBC count, R, ITGV, VC, TLC, PO2, DCO, and chest x-ray film. The unprotected challenge provoked late responses characteristic of extrinsic allergic alveolitis. In the challenge using the mask, all six patients reported to be completely free of symptoms. Compared with the test without a mask, a statistically significant reduction in the rise of temperature, WBCs, HR, R, TLC, and PO2 was observed. Compared with the initial values, a statistically significant reduced increase of temperature and leukocytes was demonstrated in the test using the mask. Pulmonary and systemic alterations were significantly reduced but not completely prevented by the application of the particle-filtering half mask.

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[14C]-labeled josamycin (Wilprafen) readily enters several types of human phagocytic cells-polymorphonuclear leucocytes (PMNLs), adherent monocytes and alveolar macrophages - and is accumulated by these cells to a concentration about 20 times that in the extracellular medium. Similar studies using [14C]-benzyl penicillin revealed that the beta-lactam antibiotic penetrated these cells very poorly. Low concentrations of josamycin and the various phagocytes acted synergistically to inhibit the intracellular proliferation of L. pneumophila or H. influenzae. In contrast, penicillin G was not effective against legionellae ingested by PMNLs, monocytes or alveolar macrophages, even at high concentrations. The uptake of the antibiotics apparently correlates well with its efficacy against the intracellular survival of bacterial pathogens in human phagocytic cells.

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