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Study objectives Pulmonary fibrosis due to lipid peroxidation is a major symptom of paraquat intoxication. Ethane in the expired breath (exEth) reflects lipid peroxidation and may be a measure of the damage effected by oxygen radicals in acute lung injury. The purpose of this study was to evaluate the clinical efficacy of exEth as a measure of exposure to paraquat and as an indicator of lung damage. Design Exposure levels were evaluated by the amount ingested, semiquantitative measurement of urine paraquat levels, and plasma paraquat concentration. End-tidal breath was collected for measurement of ethane 24 h after paraquat ingestion. Renal function and blood gas analyses were conducted on the same day as the breath collection, and the final clinical outcome was defined as either recovery or death. Associations between exEth and paraquat exposure profiles and clinical outcomes were assessed using linear regression models. Patients Twenty-one patients poisoned by paraquat were selected for the study during 2001 and 2002. Results exEth could not be used as a predictor of laboratory parameters such as Pao2, Paco2, serum creatinine, and lung injury (as graded by high-resolution CT). A logistical analysis revealed that only the amount of paraquat ingested was a significant predictor of fatality (p = 0.021). The strength of the association between exEth and fatality was unaffected by the addition of potential confounders such as age, sex, and time interval and paraquat concentration. Conclusion exEth cannot be used as either an independent predictor of survival or a specific marker of lung injury in patients with acute paraquat poisoning.

Study objectives: Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High-resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA. Patients and design: Abnormalities of the large airway (bronchial wall thickness) and small airways (prominence of centrilobular structures and air trapping) were measured semiquantitatively on HRCT scans of 24 non-NFA, 16 NFA, and 16 control subjects. In addition, these abnormalities were reevaluated after intensive and relatively long-term (> 6 months) treatment with inhaled corticosteroids. Results: Prominence of centrilobular structures was observed in 36% of mild asthma cases, in 70% of moderate-to-severe asthma cases, and in 100% of NFA cases. Prominence of centrilobular structures, but neither bronchial wall thickness nor the area of air trapping, was significantly increased in NFA, as compared with mild or moderate-to-severe asthma (p < 0.05). In the seven non-NFA and five NFA patients who underwent follow-up HRCT scans, only bronchial wall thickness was decreased significantly in the NFA cases (p < 0.05), while bronchial wall thickness and the prominence of centrilobular structures were significantly decreased in the non-NFA cases. These small airway abnormalities were partially reversible in the both groups. Residual prominence of centrilobular structures after long-term inhaled corticosteroid treatment was significantly higher in NFA than non-NFA patients. Conclusions: The results of our study indicate that extensive small airway abnormalities may be associated with NFA, and that these abnormalities are partially reversible after the successful control of asthma symptoms. (CHEST 2004; 126:1840–1848)

The immune response is impaired in patients with malignancy, and radiation therapy (RT) can exacerbate the cancer induced-attenuation of immune response. In order to search for the fine mechanisms behind the RT-induced attenuation of cell-mediated immune response, we measured the number of lymphocytes in peripheral blood, its subsets, and lymphoblast transformation induced by phytohemagglutinin (PHA), purified protein derivatives (PPD), mitogenic monoclonal antibody anti-CD3, and mitogenic combination of anti-CD2 antibodies 9-1 and 9.6 before and after RT in 19 patients with squamous cell lung cancer. Radiation therapy significantly decreased the total numbers of lymphocytes, CD-3, CD-4, and CD8-positive lymphocytes in peripheral blood. However, RT did not change the per centages of lymphocytes and its subsets. Radiation therapy increased the percentage of interleukin 2 (IL-2) receptor-positive lymphocytes, and RT significantly decreased in vitro lymphoblast transformation by PHA, PPD, or monoclonal antibodies to T-cell surface antigens (anti-CD2 or anti-CD3). In vitro incubation with IL-2 did not increase lymphoblast transformation by anti-CD3 before RT but significantly increased after RT. In conclusion, we suggest that one of the fine mechanisms behind the RT-induced suppression of immune responsiveness of patients with lung cancer is a defect in IL-2 synthesis by lymphocytes.

Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma.This study was a prospective analysis.Outpatient clinics of tertiary hospitals.Eighty-six adult outpatients with moderate-to-severe asthma.Eighty-six patients with asthma who had initial FEV1 values of80% predicted after they had received inhaled GCs (fluticasone propionate, 1,000 microg/d) for 4 weeks. The primary end points were FEV1, FEV1/FVC ratio, forced expiratory flow (midexpiratory phase), and the score at presentation in the asthma-related quality-of-life questionnaire (AQLQ).The inhalation of GCs for 4 weeks had significant improvements in the FEV1% predicted and in the AQLQ score compared with the baseline values. Asthmatic patients with responses of12% (n = 46, 53.4%) in the change in FEV1 (deltaFEV1 = [FEV1 at 4 weeks--baseline FEV1]/baseline FEV1 x 100) also had significantly higher proportions of blood eosinophils and lower FEV1 values (in liters) prior to treatment. The change in FEV1 values correlated with the number of sputum eosinophils prior to GC inhalation (r = 0.242; p0.05) and correlated inversely with the FEV1 percent predicted values prior to GC inhalation (r = -0.462; p0.001).The FEV1 percent predicted and the blood and sputum eosinophil levels prior to GC inhalation are associated with the responsiveness to inhaled GCs in patients with moderate-to-severe asthma.

Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High-resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA.Abnormalities of the large airway (bronchial wall thickness) and small airways (prominence of centrilobular structures and air trapping) were measured semiquantitatively on HRCT scans of 24 non-NFA, 16 NFA, and 16 control subjects. In addition, these abnormalities were reevaluated after intensive and relatively long-term (6 months) treatment with inhaled corticosteroids.Prominence of centrilobular structures was observed in 36% of mild asthma cases, in 70% of moderate-to-severe asthma cases, and in 100% of NFA cases. Prominence of centrilobular structures, but neither bronchial wall thickness nor the area of air trapping, was significantly increased in NFA, as compared with mild or moderate-to-severe asthma (p0.05). In the seven non-NFA and five NFA patients who underwent follow-up HRCT scans, only bronchial wall thickness was decreased significantly in the NFA cases (p0.05), while bronchial wall thickness and the prominence of centrilobular structures were significantly decreased in the non-NFA cases. These small airway abnormalities were partially reversible in the both groups. Residual prominence of centrilobular structures after long-term inhaled corticosteroid treatment was significantly higher in NFA than non-NFA patients.The results of our study indicate that extensive small airway abnormalities may be associated with NFA, and that these abnormalities are partially reversible after the successful control of asthma symptoms.

To clarify the interrelation between interleukin-2 (IL-2) and soluble IL-2R receptor (sIL-2R), as products of T-cell activation in the bronchial tree of patients with bronchial asthma, we measured the concentration of IL-2, sIL-2R, and the cellular composition in bronchoalveolar lavage (BAL) fluid. We also measured physiologic parameters, including provocation concentration of histamine required to reduce the forced expiratory volume in 1 s by 20 percent of the prechallenge baseline (PC20). The concentrations of IL-2 and sIL-2R were higher in BAL fluid of symptomatic patients with bronchial asthma than those of normal subjects and asymptomatic patients. There was a significant correlation between IL-2 and sIL-2 concentrations in BAL fluid of the patients with bronchial asthma. Patients with other lung diseases had significantly higher concentration of IL-2 than normal control; however, sIL-2R was not detected in their BAL fluids. The concentration of IL-2 inversely correlated with FEV1 in symptomatic bronchial asthma. Among the inflammatory cells in BAL fluid, percentages of eosinophils showed significant correlation with the concentrations of IL-2 and sIL-2R in BAL fluid of the patients with bronchial asthma. In conclusion, IL-2 within the bronchial tree appears to be associated with eosinophil infiltration. This leads to physiologic changes in symptomatic patients with bronchial asthma, which may be influenced by the presence of sIL-2R in BAL fluid.

The early diagnosis of diffuse infiltrative lung disease (DILD) is important in prognosis and it is necessary to develop a noninvasive, inexpensive, and rapid diagnostic tool for suspected cases of DILD. Thus, we measured the epithelial permeability via radioisotope (99mTc-DTPA) in 22 patients with DILD for clinical application of the clearance rate (T1/2LB) of radioisotope on the early diagnosis of DILD. We divided the patients with DILD into the early and late stages according to the derangements of the diffusion capacity for carbon monoxide. The T1/2LB in patients with DILD were significantly shorter when compared with those with normal control in all lobes. However, 40 to 58 percent of T1/2LB in patients with DILD overlapped normal values (2 SDs of mean of T1/2LB of normal control) dependent on specific lung regions. The T1/2LB of patients with early-stage DILD was longer than that of patients with late-stage DILD in right upper and middle lobes. Although T1/2LB of 99mTc-DTPA, the index of alveolar epithelial permeability, was shortened in patients with DILD with normal diffusing capacity, it was difficult to detect early-stage DILD by measuring alveolar epithelial permeability because of many overlaps of T1/2LB between early-stage DILD and normal control.