Associated demographics of persistent exhaled nitric oxide elevation in treated asthmatics.

BACKGROUND: The fraction of exhaled nitric oxide (FENO) is reduced by anti-inflammatory treatment in asthma. However, the FENO level is also regulated by individual demographics and there is considerable variation among clinically stable patients. OBJECTIVE: We hypothesized that some demographics may be responsible for persistent FENO elevation despite inhaled corticosteroids (ICS) therapy in asthma. METHODS: This was a prospective observational study. We initially screened 250 stable asthmatics and determined the FENO cut-off point for identifying poorly controlled asthma defined by one of the following criteria: Asthma control test <20, or forced expiratory volume in one-second % of predicted <80%, or peak expiratory flow variability <80% (Study 1). After 12-weeks, 229 patients who maintained high or low FENO were selected and the independent factors which might contribute to a high FENO were examined (Study 2). RESULTS: A FENO level >39.5 p.p.b. yielded 67% sensitivity and 76% specificity for identifying the patients with poorly controlled asthma. The persistent high FENO group (≥ 40 p.p.b.) was more likely to be ex-smokers, to show evidence of atopy (positive specific IgE, higher serum IgE and blood eosinophils), and to have allergic comorbidities. Especially, past smoking history, blood eosinophils, and chronic rhinosinusitis were identified to be independent predictors of high FENO. Neither the dose of ICS nor other medication use showed any difference between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggested that past smoking history, blood eosinophilia, and chronic rhinosinusitis are involved in the persistent airway inflammation detected by FENO. Although their relative contributions on FENO values should be further quantified, clarification of the features of the subjects with high FENO might provide clues for adjustment of the treatment approach in asthma.

Phase I study of a combination of irinotecan and ifosfamide in advanced primary lung cancer.

We sought to investigate cisplatin-free chemotherapy for patients with primary lung cancer. We therefore conducted a Phase II study to identify; a) the maximum tolerated dose (MTD) of irinotecan (CPT-11) given with a fixed dose of ifosfamide (IFM), and b) the principal toxic effects associated with this regimen in a Phase I study. A total of 27 patients with previously treated or untreated primary lung cancer received CPT-11 on days 1, 8 and 15 in combination with a fixed dose of IFM, 1.5 g/m2/day, on days 1 through 3, given every 4 weeks. The starting dose of CPT-11 was 30 mg/m2, which was increased by amounts of 10 mg/m2. Four patients were assigned to different dosage levels, and drug toxicity was evaluated for the first 2 cycles. The MTD of CPT-11 was 90 mg/m2, with leukopenia being the dose-limiting effect. The response rate was 43% (6/14; 1 complete response) in non-small cell lung cancer, and 78% (7/9; no complete response) in small cell lung cancer. The recommended dose of CPT-11 for a Phase II study is thus 80 mg/m2 on days 1, 8 and 15 with IFM 1.5 g/m2 given on days 1 through 3. This regimen appears particularly encouraging, because of its low toxicity. Phase II trials of the combination are indicated.

[Summer-type hypersensitivity pneumonitis in a family].

We encountered a family in which three of the five members (The parents and a daughter) had summer-type hypersensitivity pneumonitis that occurred in late summer. All three patients had a productive cough and shortness of breath. Chest roentgenograms of the mother and daughter (but not the father) showed diffuse small nodular shadows in both lung fields. Examination of bronchoalveolar lavage fluid from all three patients showed very high total cell counts, high percentages of T lymphocytes, and low ratios of CD4(+)-to-CD8+ cells. Microscopic examination of transbronchial biopsy specimens obtained from the daughter revealed infiltration of mononuclear cells with characteristic Masson bodies in alveolar septa, and granulomas in the interstitium. Both mother and daughter were positive for serum anti-Trichosporon cutaneum (serotype II) antibody, but the father, who was a current smoker was not. Thus, both mother and daughter were given the diagnosis of summer-type hypersensitivity pneumonitis, and in the father that diagnosis was strongly suspected.

[Chronic pulmonary paracoccidioidomyosis in a Japanese Adult].

We encountered a case of chronic pulmonary paracoccidiodomycosis in Japan. A 53-year-old Japanese man, who had worked in Brazil from 1964 to 1969. Came to our hospital because of abnormal shadows on a screening chest roentgenogram. In 1989, he had been treated with fluconazole for mucocutaneous-lymphangitic paracoccidioidomycosis with oral ulceration and neak hymphadenitis. Chest roentgenograms and computed tomograms showed diffuse small nodular and emphysematous shadows. Microscopical examination of specimens obtained by transbronchial lung biopsy showed no abnormality. He was treated with oral fluconazole, and the abnormal radiographic shadows regressed. We believe that this was the first case of chronic pulmonary paracoccidiodomycosis in Japan.

[A case of unilateral hilar lymphadenopathy resembling lung cancer due to mycoplasmal pneumonia in an adult].

A case of unilateral hilar lymphadenopathy due to mycoplasmal pneumonia in an adult patient is presented. A 54-year-old female was admitted to our hospital because of high grade fever and abnormal shadows on chest roentgenograms. She did not have any respiratory symptoms before admission. Chest roentgenograms on admission revealed a tumor-like shadow in the right hilus resembling lung cancer. On the seventh day after admission, abnormal shadows on chest roentgenograms spontaneously improved without therapy. The patient was diagnosed as having mycoplasmal infection based on the serological tests.

Rapid diagnosis of cytomegalovirus and Pneumocystis carinii pneumonia by using the capillary polymerase chain reaction.

We attempted to detect cytomegalovirus DNA (CMV-DNA) and Pneumocystis carinii DNA (P. carinii-DNA) in sputum samples of 18 hematological neoplasm patients with pneumonia, using rapid cycle DNA amplification. A thermal cycler based on recirculating hot air was used for rapid temperature control of 10-microliters samples in this glass capillary tubes. After a total amplification time of 15 min, the amplified products were electrophoresed on agarose gels and visualized with ethidium bromide. In three cases, CMV-DNA was detected at about the time the pneumonia occurred. These patients were successfully treated with ganciclovir in the early stages of infection and CMV was not detected by the virus culture method. In four other cases, P. carinii-DNA was detected in their sputum samples but not detected by Grocott staining. These four cases of P. carinii were successfully treated with sulfamethoxazole-trimethoprim. For detection of CMV-DNA and P. carinii-DNA using the capillary polymerase chain reaction (PCR), a different temperature setting base on the primer difference was not necessary. Therefore, capillary PCR was performed at the same time for detection of CMV and P. carinii. We conclude that capillary PCR amplification is a valuable tool for rapid diagnosis and early treatment of pneumonia due to CMV and P. carinii.

[Rapid diagnosis of cytomegalovirus pneumonia and Pneumocystis carinii pneumonia by using polymerase chain reaction DNA amplification].

We attempted to detect cytomegalovirus DNA (CMV-DNA) and Pneumocystis carinii DNA (carinii-DNA) in urine, blood and sputum samples of 16 leukemia patients with pneumonia, using the polymerase chain reaction (PCR). Synthetic oligonucleotide primer pair were used to amplify DNA from the major immediately genes of CMV and genes for the large subunit of mitochondrial ribosomal RNA of P. carinii. Amplified products were detected by gel electrophoresis. In two cases, CMV-DNA was detected at about the time the pneumonia occurred, and in one of the two cases, CMV-DNA was detected in the sputum sample. This patient was treated immediately with ganciclovir. After ganciclovir treatment, clinical and biochemical signs of CMV pneumonia disappeared. In three cases, carinii-DNA was detected in their sputum samples. In their blood and urine samples, carinii-DNA were not detected. This three cases were treated with sulfamethoxazole-trimethoprim and successfully treated episodes of P. carinii pneumonia. We conclude that PCR amplification may be a valuable tool for rapid diagnosing CMV pneumonia and P. carinii pneumonia.