Incidence Of Acute Exacerbation Research Articles

Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia.

The role of second-line chemotherapy in patients with non-small cell lung cancer (NSCLC) and preexisting interstitial pneumonia (IP) previously treated with platinum-based chemotherapy remains uncertain. This study was conducted to elucidate the efficacy and tolerability of second-line docetaxel monotherapy for patients with platinum-refractory advanced (stage IIIB, IV, or relapse) NSCLC and preexisting IP. A total of 35 patients (median age, 67years) treated with docetaxel monotherapy in a second-line setting following first-line platinum-based chemotherapy between January 2002 and December 2013 were retrospectively reviewed. The overall response rate and disease control rate were 8.6% [95% confidence interval (CI) 0-17.9%] and 37.1% (95% CI 21.1-53.1%), respectively. The median progression-free survival and median overall survival periods were 1.6months (95% CI 1.2-2.0months) and 5.1months (95% CI 3.2-6.7months), respectively. The incidence of acute exacerbation (AE) of IP following docetaxel monotherapy was 14.3% (5/35 patients). Of the five patients who developed AE of IP, three patients died. The toxicity of this regimen was substantial, with treatment-related deaths occurring in 5 (14.3%) patients (AE of IP: 3, sepsis: 2). Docetaxel monotherapy has a poor activity and substantial risks when used for the treatment of platinum-resistant NSCLC with IP. Novel therapeutic approaches should be explored in this setting.

Usefulness of a disease severity staging classification system for IPF in Japan: 20 years of experience from empirical evidence to randomized control trial enrollment.

Since 1991, the severity of idiopathic pulmonary fibrosis (IPF) has been classified into 4 stages-stage I (characterized by a resting PaO2 ≥ 80 Torr), stage II (70-79 Torr), stage III (60-69 Torr), or stage IV (<60 Torr)-to aid decisions on medical care subsidization in Japan. Among patients with stage II/III IPF, the severity should be increased by one stage if the lowest oxygen saturation on pulse oximetry (SpO2) is <90% during a 6-min walk test. Patients with stage III/IV IPF receive Japanese government subsidies for incurable diseases. This classification system highly correlates with serial changes in the percentage of vital capacity (%VC), the diffusing capacity for carbon monoxide, the incidence of acute exacerbation, and survival. A phase III trial of pirfenidone showed that IPF patients with an SpO2 on exertion of <90% and either a %VC ≥ 70% or a PaO2 ≥ 70 Torr (which includes most patients with stage III disease) at baseline would benefit from pirfenidone treatment. Recent post-marketing surveillance of 1370 patients--67.3% of whom had stage III/IV IPF--showed that pirfenidone was well-tolerated among those treated for longer than 6 months (63% of patients). A Japanese randomized controlled trial (RCT) demonstrated that inhaled N-acetylcysteine monotherapy benefitted patients with early IPF (stage I/II, with no desaturation on exertion). Thus, N-acetylcysteine monotherapy is suitable for early IPF, and pirfenidone is indicated for advanced disease. The classification of IPF severity is important in identifying clinically responsive patients and those suitable for RCT enrollment.

Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis

Acute exacerbation (AE) is a major cause of death in idiopathic pulmonary fibrosis (IPF). However, little is known about sensitive biomarkers for predicting AE. The aim of our study was to investigate the significance of KL-6 and CC-Chemokine Ligand 18 (CCL18) as predictors for AE of IPF. We prospectively collected a total of 77 patients with IPF. Serum levels of KL-6 and CCL18 were measured by ELISA. The correlation between baseline serum levels of the markers and the incidence of AE was evaluated. Thirteen (17%) patients experienced AE during follow-up. Baseline serum KL-6 levels were significantly higher in patients who developed AE than in patients with stable IPF (p<0.0001), whereas serum CCL18 levels showed no difference between these groups (p=0.13). At a cut-off level of 1300U/mL for KL-6, the sensitivity, specificity, accuracy and likelihood ratio to predict AE were 92%, 61%, 66% and 2.36, respectively. In the Kaplan-Meier analysis, patients with baseline serum KL-6 level ≥1300U/mL experienced earlier onset of AE (p=0.002), whereas CCL18 showed no predictive value (p=0.11). In the multivariate analysis, baseline serum KL-6 (both continuous and at a cut-off level of ≥1300U/mL) was an independent predictive factor for AE after adjustment for age, sex, smoking history and %vital capacity (hazard ratio=1.001, 18.8; p=0.010, 0.008, respectively). Baseline serum KL-6 level is a sensitive predictor for the onset of AE in IPF.

Soluble receptor of advanced glycation end-products and endothelial dysfunction in COPD

Chronic obstructive pulmonary disease (COPD) is accompanied by an increased cardiovascular risk which is aggravated by the incidence of acute exacerbations (AE). Endothelial function, as well as the soluble receptor for advanced glycation end-products (sRAGE), both markers of cardiovascular risk, has been shown to be decreased in stable COPD. We aimed to investigate a possible link between sRAGE and endothelial function in AE of COPD. We hypothesize that circulating levels of sRAGE and endothelial function are impaired during AE and improve after clinical recovery, respectively. We enrolled patients admitted to hospital due to an AE of COPD without overt cardiovascular comorbidities. Study related procedures comprised spirometry, measurement of plasma sRAGE levels and the quantification of endothelial function by means of the flow-mediated dilation technique (FMD). All measurements were scheduled during hospitalization and after confirmed clinical stability. We recruited 29 patients (27% female) with moderate to severe COPD. Median sRAGE concentration was 525 pg/mL (371-770, 1st-3rd quartile) and mean FMD 6.7 ± 3.6% at AE. There was a significant increase of sRAGE levels to 876 pg/mL (633-1371, 1st-3rd quartile, p < 0.001) and a simultaneous improvement in FMD (10.0 ± 3.4%, p < 0.001) after clinical recovery. There was a significant positive association between sRAGE and FMD (regression coefficient = 2.43; p = 0.01) in our study sample. Our results indicate a substantial decrease in sRAGE levels and endothelial function during AE, with evidence of improvements after clinical recovery. sRAGE may contribute to cardiovascular risk in COPD.

The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis--a randomised controlled trial.

BackgroundExercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis.MethodsParticipants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months.ResultsEighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1–3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1–3]) compared to the control group (2[1–3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047).ConclusionsExercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months.Trial registryClinicalTrials.gov (NCT00885521).

Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study

ObjectivesTo investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).DesignA retrospective case–control study.SettingA single academic hospital.Participants51 consecutive patients diagnosed...

병리특이적 형태분석 기법을 이용한 HRCT 영상에서의 새로운 봉와양폐 자동 분할 방법

봉와양폐(Honeycomb)는 직경 2~10mm 정도의 크기가 같지 않은 낭포(Cyst)가 경계가 명확한 섬유질(Fibrosis)로 이루어진 벽에 둘러싸여 밀집된 형태로 이루어져 있다. 봉와양폐가 발견될 경우 급성악화의 발생 빈도가 높으며 따라서 봉와양폐의 관찰 여부와 측정은 임상에서 중요한 지표가 된다. 따라서 본 논문에서는 봉와양폐 영역의 정량적 측정을 위하여 봉와양폐의 특징을 이용한 형태학적 기법과 군집성 평가 기법을 통해 자동 구획 방법을 제안하였다. 첫 번째로 영상의 잡음을 제거하기 위하여 가우시안 필터링을 적용하고, 모폴로지 기법 중 팽창 기법을 이용하여 폐 영역을 구획하였다. 두번째로, 주변 8방향 검사를 통해 봉와양폐를 구성하는 낭포의 후보군을 찾고, 영역 확장과 외곽선 검사를 통해 비 낭포들을 제거하였다. 마지막으로 군집화 검사를 통해 최종적으로 봉와양폐를 구획하였다. 제안한 방법은 80장의 고해상도 컴퓨터 단층촬영 영상에서 실험한 결과, 89.4%의 민감도와, 72.2%의 양성 예측도를 보였다. Honeycombs are dense structures that small cysts, which generally have about 2~10 mm in diameter, are surrounded by the wall of fibrosis. When honeycomb is found in the patients, the incidence of acute exacerbation is generally very high. Thus, the observation and quantitative measurement of honeycomb are considered as a significant marker for clinical diagnosis. In this point of view, we propose an automatic segmentation method using morphological image processing and assessment of the degree of clustering techniques. Firstly, image noises were removed by the Gaussian filtering and then a morphological dilation method was applied to segment lung regions. Secondly, honeycomb cyst candidates were detected through the 8-neighborhood pixel exploration, and then non-cyst regions were removed using the region growing method and wall pattern testing. Lastly, final honeycomb regions were segmented through the extraction of dense regions which are consisted of two or more cysts using cluster analysis. The proposed method applied to 80 High resolution computed tomography (HRCT) images and achieved a sensitivity of 89.4% and PPV (Positive Predictive Value) of 72.2%.

Chemotherapy for non-small cell lung cancer complicated by idiopathic interstitial pneumonia

Idiopathic interstitial pneumonia (IIP) is considered to be one of the risk factors for lung cancer (LC). However, therapeutic options for patients with LC complicated by IIP are not well established. In this study, we investigated the feasibility and efficacy of chemotherapy for patients with non-small cell lung cancer (NSCLC) complicated by IIP (NSCLC-IIP). We retrospectively analyzed 22 NSCLC-IIP patients who received chemotherapy. To determine how IIP affected the clinical outcomes in NSCLC, they were compared with 276 NSCLC patients without IIP, who were treated with chemotherapy alone. The response rate (partial response + stable disease) was 72.3% (17/22), whereas the incidence of acute exacerbation (AE) was 13.6% (3/22) in NSCLC-IIP patients treated with chemotherapy. NSCLC-IIP patients had significantly shorter survival compared with NSCLC patients without IIP (P<0.001) following chemotherapy, although the response rates to chemotherapy were not significantly different between the two groups. Multivariate analysis demonstrated that, in NSCLC patients receiving chemotherapy, IIP was a significantly unfavorable factor for progression-free and overall survival. Despite similar response rates to chemotherapy, NSCLC-IIP patients showed poorer prognosis than NSCLC patients without IIP, possibly due to the natural course of IIP. Chemotherapy may be a feasible option for NSCLC-IIP, if the risks of adverse effects are acceptable.

Acute Exacerbation of Usual Interstitial Pneumonia After Resection of Lung Cancer

Acute exacerbation of usual interstitial pneumonia is one of the most life-threatening complications after resection of lung cancer. It is important to detect patients at high risk for acute exacerbation. The purpose of this study was to investigate the incidence of postoperative acute exacerbation and the importance of the finding of honeycombing in predicting the risk of it. From 992 consecutive pulmonary resections for lung cancer, the background lung was retrospectively assessed histologically. Preoperative chest computed tomographic images of those patients with histologically proven usual interstitial pneumonia were retrospectively reassessed and classified into three groups: typical honeycombing, possible honeycombing, and no honeycombing. Records of patients who experienced postoperative acute exacerbation were extracted from the clinical database, and the correlation between computed tomographic findings and incidence of acute exacerbation was analyzed. Of the 992 lung cancer patients, 12 (1.2%) experienced postoperative acute exacerbation. Usual interstitial pneumonia was histologically confirmed in 249 patients, and 4.8% of them experienced postoperative acute exacerbation. No patient without usual interstitial pneumonia experienced it. Preoperative computed tomographic images were available in 205 of the 249 patients. Postoperative acute exacerbation developed in 13.6% of patients (6 of 44 patients) in the typical honeycombing group, 6.4% of patients (5 of 78 patients) in the possible honeycombing group, and 0% of patients (0 of 83 patients) in the no-honeycombing group. Compared with the no-honeycombing group, the incidence of acute exacerbation in the typical and possible honeycombing groups was significantly higher (p=0.001, p=0.025, respectively). Physicians should consider the finding of possible honeycombing, as well as typical honeycombing, a potential risk factor for acute exacerbation after pulmonary resection for lung cancer.

Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients. 70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation. Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS > 3, 6-min walking distance ≤ 72% predicted and composite physiologic index > 41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients. In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.

Incidence of Acute Exacerbation of Interstitial Pneumonia in Operated Lung Cancer: Institutional Report and Review

Several small studies have reported that acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer, though the incidence rate is unclear. We examined our institutional data and performed a search of the MEDLINE database for publications regarding AE of IIP following surgery for lung cancer. Studies reporting the incidence rates of IIP and AE were included. Eleven studies including our institutional data were determined to be eligible. Seven studies designated the incidence of IIP. Of 4749 patients (from 7 studies) who underwent lung resection for NSCLC, 277 had IIP, for an incidence rate of 5.8% (range 1.1%-11.7%). Eleven studies designated the incidence of AE from IIP patient, 67 (15.8%) of 424 IIP patients (from 11 studies) developed AE after surgery, of whom 38 (56.7%) died during the postoperative course. Coexistent IIP in patients with lung cancer increases the risk of lung cancer surgery. Furthermore, AE of IIP may be a major cause of operation-related death.

Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome

Although acute exacerbation of idiopathic pulmonary fibrosis (IPF) has become well recognised, the reported incidence and outcomes are highly variable, and risk factors are unknown. The aim of this study was to estimate the incidence, risk factors and impact of acute exacerbations, and other known causes of rapid deterioration. This was a retrospective review of 461 patients with IPF (269 cases were biopsy-proven). The median follow-up period was 22.9 months. Rapid deterioration requiring hospitalisation occurred in 163 (35.4%) patients, with multiple episodes in 42 patients. Acute exacerbation was the most frequent cause (55.2%), followed by infection. The 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low forced vital capacity (FVC) were significant risk factors. The in-hospital mortality rate was 50.0%, and the 1- and 5-yr survival rates from the initial diagnosis were 56.2 and 18.4%, respectively. Acute exacerbation was a significant predictor of poor survival after the initial diagnosis, along with increased age, low FVC and diffusing capacity of the lung for carbon monoxide, and steroid use with or without cytotoxic therapy. 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low FVC were risk factors. Acute exacerbation had a serious impact on the overall survival of the patients with IPF.

Predictive factors for postoperative acute exacerbation of interstitial pneumonia combined with lung cancer

Postoperative acute exacerbation (AE) of usual interstitial pneumonia (UIP) is a serious complication in the surgical treatment for primary lung cancer combined with UIP. The purpose of this study was to determine the predictors of AE of UIP after a major lung resection. We retrospectively collected data for 40 patients who had been operated on for lung cancer and were diagnosed as UIP based on postoperative histopathological diagnosis. We then evaluated some predictive factors related to the AE of UIP. The incidence of postoperative AE of UIP was 15% (6/40 patients). No correlation between patients who developed AE of UIP and those who did not, in terms of preoperative C-reactive protein, white blood cell count, percentage lymphocytes, forced expiratory volume in 1 s, percentage total lung capacity, percentage diffusing capacity of lung for carbon monoxide, and the alveolar partial pressures of oxygen and carbon dioxide. Preoperative serum lactate dehydrogenase (LDH) and serum KL-6 were significantly higher and the percent vital capacity (%VC) was significantly lower in patients who developed AE of UIP than in those who did not. Furthermore, recursive descent partition analysis revealed that %VC (<80.6%) and LDH (>or=241 IU/l) could distinguish patients with AE from those without AE. Preoperative %VC plus serum LDH values were considered the predictive factors for AE of UIP after surgery for lung cancer.

Association between incidence of acute exacerbation and medication therapy in patients with COPD

Background:As exacerbations of chronic obstructive pulmonary disease (COPD) significantly worsen patients’ health status and increase disease-related mortality, greater control of exacerbations has important implications for improving patients’ health and survival. The incremental benefits of pharmacologic therapies in preventing COPD exacerbations remain unclear. The objective of this observational study was to examine the risk of COPD-related exacerbations between groups of patients receiving inhaled corticosteroids (ICS), anticholinergics (AC), long-acting β2-agonists (LABA), or fixed-dose combinations of ICS and LABA.Methods:A 12-month retrospective cohort analysis of 2923 patients, who were at least 40 years old with the first time COPD in 12 months (i.e., no COPD for 12 months prior to this time) between 2000 and 2004, was conducted using the MarketScan research databases. Patients with at least two prescriptions for ICS, AC, LABA, or ICS + LABA during the observation period were followed from the index prescription date for the duration of the study. COPD-related exacerbations were defined as clinical events in which a primary diagnosis for a respiratory condition had resulted in hospitalization, an emergency room visit, or an outpatient visit followed by a prescription fill of oral corticosteroids or antibiotics within 14 days of the visit. Exacerbation rates were evaluated using a Cox proportional hazard model with adjustment for age, gender, comorbidities, hospitalizations, emergency room visits, and the number of outpatient visits.Findings:Compared with ICS alone, COPD exacerbation rates were 35% (CI:22–42%) lower with ICS + LABA, 32% (CI:13–43%) lower with LABA, and 28% (CI:15–36%) lower with AC. The hazard ratio of the first observed COPD exacerbation was 13–18% lower with the use of bronchodilators, with or without ICS, than with ICS alone. In addition, patients receiving ICS alone experienced more exacerbations during the 12-month period following initiation of therapy than those patients receiving LABA, AC, or ICS + LABA. Generalizability of the results and randomization of treatments were limited due to nature of the administrative claim databases.Conclusion:The present study found that use of bronchodilators, with or without ICS, in COPD patients resulted in a lower exacerbation rate when compared with ICS monotherapy. Further research is required to understand the clinical effects of specific pharmacologic therapies on COPD exacerbations, as well as their impact on long-term outcomes and costs.

Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases

BackgroundAcute exacerbation (AE) is currently established as a distinct condition with acute deterioration of respiratory status in idiopathic pulmonary fibrosis (IPF). Recently, several studies have reported that AE also occurred in interstitial pneumonias other than IPF, such as collagen vascular disease-associated interstitial pneumonia (CVD-IP). However, the incidence of AE in CVD-IP and its clinical characteristics remain to be fully determined. This study was conducted to elucidate cumulative incidence of AE in CVD-IP and its clinical features.MethodsWe reviewed 83 biopsy-proven CVD-IP patients, estimated cumulative incidence of AE, and examined its clinical characteristics.ResultsAmong 83 CVD-IP patients, six patients with a mean age of 65.7 years developed AE (overall incidence, 7.2%; 1-year incidence, 1.25%). Underlying CVDs included rheumatoid arthritis (RA) (n = 5; overall incidence, 20.0%) and primary Sjögren syndrome (n = 1; overall incidence, 5.9%). Patients with AE showed acute respiratory deterioration with severe hypoxemia (mean PaO2/FiO2 ratio, 131). Radiologically, ground-glass opacity was superimposed on the underlying reticular abnormalities. Preexisting histological patterns included three usual interstitial pneumonia (UIP) and two non-specific interstitial pneumonia (NSIP). Five (83.3%) of six patients died of respiratory failure despite intensive therapy. Univariate Cox's proportional hazards analysis showed that age and RA diagnosis were significantly associated with AE. Multivariate Cox's proportional hazards analysis indicated that age was an independent significant factor predicting AE.ConclusionsThese data suggest that AE can occur in CVD-IP, and this condition is closely similar to that of IPF with poor prognosis. AE is most common in RA, and associated with higher ages.

Stopping lamivudine therapy after biochemical breakthrough may be a feasible option in selected HBeAg‐positive patients

Drug resistance remains a major problem during lamivudine treatment for patients with hepatitis B virus infection. Continuing or stopping lamivudine in patients with biochemical breakthrough is an issue that has not been investigated extensively. Particularly, HBeAg seroconversion and its durability achieved in these settings have never been studied so far. In this study, we compared the clinical outcomes including HBeAg seroconversion in hepatitis B e antigen (HBeAg)-positive patients who either continued or stopped lamivudine treatment after biochemical breakthrough. This was a retrospective cohort study of 73 consecutive patients with biochemical breakthrough followed up for at least 12 months. Of these, 35 (Group I) stopped and the remaining 38 (Group II) continued lamivudine therapy after breakthrough. During 12 months, there was a tendency towards higher rates of HBeAg seroconversion in Group I compared with Group II (P = 0.078). By multivariate analysis, age >or=45 years and acute exacerbation within 6 months of stopping lamivudine were the two independent predictors of HBeAg seroconversion for Group I (P = 0.034 and P = 0.012, respectively). There was no difference in the overall incidence of acute exacerbation and hepatic decompensation between the two groups (P = 0.333 and P = 0.555, respectively). Six patients (17.1%) in Group I developed hepatic decompensation, for which bilirubin >or=1.2 mg/dl was an independent predictor (P = 0.002). The therapeutic gain in continuing lamivudine for biochemical breakthrough is questionable. This study suggests that discontinuation of lamivudine may be an option in older patients with normal bilirubin level.

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C.

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/ b ratio was 1-5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5-10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis.

Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: A meta-analysis of published double-blind, placebo-controlled clinical trials

Objective This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. Background Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials. Methods The trials included in this analysis were selected from a MEDLINE ® search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy ≥ 2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome. Results Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study), ≥ 5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was −1.37 (95% CI, −1.5 to −1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of −0.32 clinical event (95% CI, −0.50 to −0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo). Conclusion These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

65. The Evolution of the Prehospital Care of Pediatric Asthma

Purpose: The prevalence of asthma in the pediatric population is approximately 9% and the incidence of acute exacerbation in this population has been increasing. The purpose of this study was to determine if there has been a change in the pre-hospital presentation and treatment of pediatric asthma.Methods: This observational study was a retrospective consecutive case series comparing pediatric (#18 yrs) asthmatics treated and transported by an inner city EMS system over two years. (1987, 1992). Data collected included patient demographics, prehospital treatment, and evaluated diagnostic criteria used by paramedics to initiate treatment. Students t test was performed for continuous data and contingency analysis (chisquare) for non-continuous data. A Wilks stepwise discriminant analysis was performed on 1987 and 1992 data to evaluate diagnostic factors.Results: There were 407 transports in 1987 and 652 in 1992, representing a 60% increase. 237(56%) of patients received advanced life support (ALS) in 1987 and 344(53%) in 1992. Mean age of ALS patients in 1987 was 10.25 (±5.3) and was 8.03 (±2.8) in 1992 (p &lt;0.001). Albuterol inhalation supplanted epinephrine (1987-205, 1992-1) and aminophylline (1987-15, 1992-1) as the treatment for asthma in our service system. The discriminant analysis revealed that in 1987, paramedics treatment decision making was influenced by age, cough, cold, and/or fever, home medications, accessory muscles, absence of wheezing, and normal respiratory rate. This changed in 1992 where only the presence or absence of wheezing and accessory muscle-use to be highly correlated with treatment decisions.

Long-Term Effects of Ofloxacin on Clinical Courses in Patients with Diffuse Panbronchiolitis

To ascertain the long-term effects of ofloxacin (OFX) on clinical parameters in cases of diffuse panbronchiolitis (DPB), we treated 18 patients with this disease with OFX and compared the clinical findings before and after treatment. Pulmonary function tests including percent vital capacity, arterial oxygen tension and arterial-alveolar oxygen tension difference significantly improved with OFX. In addition, the incidence of acute exacerbation and the duration of hospitalization were reduced. These observations indicate that OFX is a useful drug for the management of chronic respiratory infections such as DPB.