Incidence Of Interstitial Lung Diseases Research Articles

Comparison between OK-432 and Talc for pleurodesis in patients with persistent pulmonary air leak: a Japanese nationwide retrospective database study.

OK-432 (Picibanil®) and talc are used in patients with persistent pulmonary air leaks. However, it is unclear which of these two agents is more effective. This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. Patients with pneumothorax who underwent chemical pleurodesis between July 2010 and March 2022 were included in this study. The patients were categorized into two groups: the OK-432 and talc groups. The primary outcome measure was treatment failure, defined as a composite of requirement for additional surgical procedures, bronchoscopic interventions, or chemical pleurodesis. The secondary outcome measures were in-hospital mortality, length of hospital stay, 30-day readmission, and incidence of interstitial lung diseases after hospitalization. To compare the outcomes between the groups, 1:4 propensity score matching was conducted. Among the 4179 eligible patients, 3551 and 628 patients underwent chemical pleurodesis using OK-432 and talc, respectively. Propensity score matching yielded 2508 and 627 patients who underwent chemical pleurodesis using OK-432 and talc within seven days of admission, respectively. The frequency of treatment failure in the talc group (37.5% vs. 31.4%; P = 0.006) was lower than that in the OK-432 group with no significant differences in other outcomes. Medical professionals can consider talc as the initial pleurodesis agent for patients with persistent air leaks.

Relative incidence of interstitial lung diseases in Brazil.

To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

The Peptide DHα-(4-pentenyl)-ANPQIR-NH2 Exhibits Antifibrotic Activity in Multiple Pulmonary Fibrosis Models Induced by Particulate and Soluble Chemical Fibrogenic Agents.

Interstitial lung diseases (ILDs) are a group of restrictive lung diseases characterized by interstitial inflammation and pulmonary fibrosis. The incidence of ILDs associated with exposure to multiple hazards such as inhaled particles, fibers, and ingested soluble chemicals is increasing yearly, and there are no ideal drugs currently available. Our previous research showed that the novel and low-toxicity peptide DHα-(4-pentenyl)-ANPQIR-NH2 (DR3penA) had a strong antifibrotic effect on a bleomycin-induced murine model. Based on the druggability of DR3penA, we sought to investigate its effects on respirable particulate silicon dioxide (SiO2)- and soluble chemical paraquat (PQ)-induced pulmonary fibrosis in this study by using western blot, quantitative reverse-transcription polymerase chain reaction (RT-qPCR), immunofluorescence, H&E and Masson staining, immunohistochemistry, and serum biochemical assays. The results showed that DR3penA alleviated the extent of fibrosis by inhibiting the expression of fibronectin and collagen I and suppressed oxidative stress and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Further study revealed that DR3penA may mitigate pulmonary fibrosis by negatively regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and mitogen-activated protein kinase (MAPK) pathway. Unexpectedly, through the conversion of drug bioavailability under different routes of administration, DR3penA exerted antifibrotic effects equivalent to those of the positive control drug pirfenidone (PFD) at lower doses. In summary, DR3penA may be a promising lead compound for various fibrotic ILDs. SIGNIFICANCE STATEMENT: Our study verified that DHα-(4-pentenyl)-ANPQIR-NH2 (DR3penA) exhibited positive antifibrotic activity in pulmonary fibrosis induced by silicon dioxide (SiO2) particles and soluble chemical paraquat (PQ) and demonstrated a low-dose advantage compared to the small-molecule drug pirfenidone (PFD). The peptide DR3penA can be further developed for the treatment of multiple fibrotic lung diseases.

Incidence, prevalence, and national burden of interstitial lung diseases in India: Estimates from two studies of 3089 subjects.

Background and objectiveThe epidemiology of interstitial lung diseases (ILDs) in developing countries remains unknown. The objective of this study was to estimate the incidence, prevalence, and national burden of ILDs in India.MethodsData of consecutive subjects (aged >12 years) with ILDs included in a registry between March 2015 and February 2020 were analyzed retrospectively. The proportion of each ILD subtype was determined. The crude annual incidence and prevalence of ILDs for our region were estimated. Subsequently, the primary estimates of the national annual incident and prevalent burden of ILD and its subtypes were calculated. Alternative estimates for each ILD subtype were calculated using the current and a large, previous Indian study (n = 1,084). Data were analyzed using SPSS version 22 and are presented descriptively.ResultsA total of 2,005 subjects (mean age, 50.7 years; 47% men) were enrolled. Sarcoidosis (37.3%) was the most common ILD subtype followed by connective tissue disease (CTD)-related ILDs (19.3%), idiopathic pulmonary fibrosis (IPF, 17.0%), and hypersensitivity pneumonitis (HP, 14.4%). The crude annual incidence and prevalence of ILDs were 10.1–20.2 and 49.0–98.1, respectively per 100,000 population. The best primary estimates for the crude national burden of all ILDs, sarcoidosis, CTD-ILD, IPF, HP, and other ILDs (in thousands) were 433–867, 213–427, 75–150, 51–102, 54–109, and 39–78. The respective alternative estimates (in thousands) were sarcoidosis, 127–254; CTD-ILD, 81–162; IPF, 46–91; HP, 130–261; other ILDs, 49–98.ConclusionIn contrast to developed countries, sarcoidosis and HP are the ILDs with the highest burden in India.

Interstitial lung disease incidence and mortality in the UK and the European Union: an observational study, 2001-2017.

ObjectiveTo compare the trends in age-standardised incidence and mortality from interstitial lung diseases (ILD) in the UK and the European Union (EU).MethodsThis was an observational study using data obtained from the Global Burden of Disease Study on residents of the UK and of the 27 EU countries. The main outcome measures were ILD age-standardised incidence rates per 100 000 (ASIR), age-standardised death rates per 100 000 (ASDR) and mortality-to-incidence ratios (MIRs), which are presented for men and women separately for each country for the years 2001–2017. Trends were analysed using joinpoint regression analysis.ResultsIn 2017, the median incidence of ILD was 7.22 (IQR 5.57–8.96) per 100 000 population for men and 4.34 (IQR 3.36–6.29) per 100 000 population for women. In 2017, the median ASDR attributed to ILD was 2.04 (IQR 1.13–2.71) per 100 000 population for men and 1.02 (0.68–1.37) per 100 000 population for women. There was an overall increase in ASDR during the observation period, with a median increase of +20.42% (IQR 5.44–31.40) for men and +15.44% (IQR −1.01–31.52) for women. Despite increases in mortality over the entire observation period, there were decreasing mortality trends in the majority of countries at the end of the observation period (75% for men and 86% for women).ConclusionOver the past two decades, there have been increases in the incidence and mortality of ILD in Europe. The most recent trends, however, demonstrate decreases in mortality from ILD in the majority of European countries for both men and women. These data support the ongoing improvements in the diagnosis and management of ILD.

Drug Repurposing Prediction and Validation From Clinical Big Data for the Effective Treatment of Interstitial Lung Disease.

Interstitial lung diseases (ILDs) are a group of respiratory disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitial tissues. Although the etiology of ILD remains unclear, some drug treatments are among the primary causes of ILD. In the present study, we analyzed the FDA Adverse Event Reporting System and JMDC Inc. insurance claims to identify a coexisting drug that reduced the incidence of ILD associated with the use of an anti-arrhythmic agent, amiodarone, and found that the thrombin inhibitor dabigatran prevented the amiodarone-induced ILD in both clinical datasets. In an experimental validation of the hypothesis, long-term oral treatment of mice with amiodarone caused a gradual decrease in body weight caused by respiratory insufficiency. In the lungs of amiodarone-treated mice, infiltration of macrophages was observed in parallel with a delayed upregulation of the platelet-derived growth factor receptor α gene. In contrast, co-treatment with dabigatran significantly attenuated these amiodarone-induced changes indicative of ILD. These results suggest that dabigatran is effective in preventing drug-induced ILD. This combinatorial approach of drug repurposing based on clinical big data will pave the way for finding a new treatment with high clinical predictability and a well-defined molecular mechanism.

Clinical Characteristics of Secondary Immune Thrombocytopenia Associated With Primary Sjögren's Syndrome.

Objective: Clinical characteristics of immune thrombocytopenia (ITP) associated with primary Sjögren's syndrome (pSS) have not been clearly defined. This study aimed to evaluate the prevalence and clinical characteristics of secondary ITP in patients with pSS.Methods: 291 pSS patients in our hospital were retrospectively analyzed. Clinical manifestations and laboratory findings were compared between pSS patients with and without ITP.Results: The prevalence of secondary ITP in pSS patients was 12.03%. Compared to pSS patients without ITP, pSS patients with ITP were younger and had higher disease activity. The prevalence of interstitial lung diseases (ILD) was significantly lower in pSS patients with ITP (30.43 vs. 54.95%; P = 0.029), and it was the same with arthritis (17.14 vs. 3.9.11%; P = 0.014) and dry eye (33.33 vs. 54.17%, P = 0.027) compared with those without ITP. Serum creatinine level was lower in pSS patients with ITP (P = 0.009), while positivity of anti-histone autoantibodies was higher in pSS patients with ITP (P = 0.025).Conclusion: This study is an initial report describing clinical features of ITP in pSS. The lower incidence of ILD and arthritis among pSS patients with ITP indicated potential active roles of platelets in the pathogenesis of fibrosis or inflammatory arthritis, which may open the way for further experimental and clinical work.

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype.

The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype. Possible reasons may include the heterogeneous nature of the aetiology, the complexity of diagnosis (and subsequent documentation of cases) and the methods employed to retrospectively analyse patient databases. This review presents a broad overview of the epidemiological data available for ILDs that may present a progressive-fibrosing phenotype, collectively and stratified according to clinical classification. We also note where further data are needed in comparison to the well-studied IPF indication.

Estimating the incidence of interstitial lung diseases in the Cree of Eeyou Istchee, northern Québec.

BackgroundLittle is known about the epidemiology of interstitial lung disease (ILD) amongst Canada’s Indigenous populations. Clinicians working in Eeyou Istchee (the Cree territory of the James Bay region of Québec, population 17, 956) suspected that ILD was more common in this area. We sought to identify all prevalent and incident cases of ILD in Eeyou Istchee between 2006 and 2013, to describe characteristics of affected patients, distribution of subtypes, and estimate disease incidence.MethodsPotential ILD cases amongst Eeyou Istchee residents were identified by searching hospitalization databases and lists of patients on long term home oxygen in the region’s nine communities, and surveying physicians and nurses. Clinical, radiological and pathological data were reviewed. Potential cases were classified as ‘Definite ILD’ if an open lung biopsy demonstrated ILD or, in the absence of histopathologic confirmation, if their thoracic CT imaging was deemed consistent with ILD by a panel of two respirologists and a chest radiologist. Potential cases for whom CT images could not be retrieved for our review were not eligible for classification as Definite ILD, unless they had undergone open lung biopsy. The Definite ILD group was further categorized by subtype of ILD. For usual interstitial pneumonia and non-specific interstitial pneumonitis patterns, we assumed cases were idiopathic in the absence of documentation of connective tissue disease or occupational exposures in the medical chart. For Definite ILD and the most common subtype, we calculated the average annual incidence rates, age-standardized to the province of Quebec, for 2006 to 2013, using a gamma distribution to calculate 95% confidence intervals.ResultsOf 167 potential cases, 52 were categorized as Definite ILD: 14 on the basis of histopathology and 38 on the basis of CT imaging alone. Six patients had a prior history of connective tissue disease. Information on occupation was recorded in the charts of 18/52 (35%) cases, and missing in the remainder. We found the most common subtype was idiopathic pulmonary fibrosis (27/52, 52%), followed by idiopathic non-specific interstitial pneumonia (13/52, 25%), and secondary usual interstitial pneumonia associated with connective tissue diseases (5/52, 10%). The age-standardized annual incidence between 2006–2013 was 80 per 100,000 person-years observed (PYO) for ILD, and 46 per 100,000 PYO for idiopathic pulmonary fibrosis.InterpretationThe incidence of ILD and of idiopathic pulmonary fibrosis in Eeyou Istchee may be higher than rates reported in other populations; however, cautious interpretation is required due to the lack of histopathological confirmation in the majority of cases, and our reliance on chart review to exclude secondary causes. A prospective study of incident cases with standardized assessments to establish the types of ILD and to assess for potential causes could overcome some of the limitations of the present analysis. Studies evaluating ILD incidence and subtype distribution in other Indigenous populations would also be of interest.

Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.

The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/105 and incidence: 19.4/105/year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/105 for sarcoidosis, 12.1/105 for CTDs-ILDs and 8.2/105 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/105 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France.

Epidemiology and distribution of interstitial lung diseases in Turkey

There is very few data on the epidemiological features of interstitial lung diseases (ILD) in the literature. These studies on this subject suffer from limited number of patients. The goal of this study was to evaluate the epidemiological features of ILD in Turkey. Fifty-four investigators, 31 centres in 19 cities from six regions of Turkey, participated in the study. Two thousand two hundred forty-five newly diagnosed patients (51.8% females), led by Turkish Thoracic Society Clinical Problems Study Group, enrolled in this prospective study. The mean age was 51.8 ± 16.7 years. The mean age among males was 50.5 ± 18.6 years and 53.0 ± 14.6 years among females (P < 0.001). 23.8% of the cases had ILD with known causes, while 39.4% were in granulomatous group, 23.7% were idiopathic, and 4.4% were in the unclassified group. Overall, histopathologically confirmed diagnosis rate was 40.4%. Sarcoidosis was the most common disease (37%), whereas cases with idiopathic pulmonary fibrosis (IPF) constituted 19,9% of patients. 53% of the sarcoidosis patients were females, and the ratio reaches to 75% under 50 years of age (for this group, IPF ratio is %3). In contrast, sarcoidosis and IPF ratios were equal in males (25%). Sarcoidosis was 8% in men over 50, while IPF was %45. The overall incidence of ILD in Turkey was computed to be 25.8/100,000.

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer.

ObjectiveCetuximab (Erbitux®) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval.MethodsAll patients to be treated with cetuximab were enrolled by the central enrolment method. Data on treatment status, and incidence and severity of adverse drug reactions were collected. The target number of patients was 1800.ResultsA total of 2126 patients were enrolled from 637 institutions. Among 2006 patients analysed, 93.2% received cetuximab as third-line or later treatment. The median duration of treatment was 15.3 weeks, and 11.1% of patients received treatment for >48 weeks. The incidence of adverse drug reactions was 89.6%, of which ≥grade 3 was 21.5%. The incidence of infusion reactions was 5.7% (any grade), with 83.3% of them occurring at the first administration. The incidence of skin disorders was 83.7% (any grade), and the time to event varied for each skin disorder. The incidence of interstitial lung diseases was 1.2% (any grade). Diarrhoea and haematotoxicity scarcely occurred with cetuximab alone.ConclusionsIn this surveillance, the incidence and categories of adverse drug reactions are not distinct from previous reports. Although most patients received cetuximab as third-line or later treatment, treatment was maintained with a median duration of 15 weeks. Cetuximab treatment in practical use is considered to be well tolerated and clinically useful in Japanese patients with metastatic colorectal cancer.

Essential efficacy and safety profiles of everolimus in Japanese patients with metastatic renal cell carcinoma.

e15140 Background: Although the efficacy of sorafenib and sunitinib was similar in Asian and non-Asian patients with metastatic renal cell carcinoma (mRCC), large differences have been shown in the incidence of adverse events (AEs) in these populations. Due to limited data obtained from the RECORD-1 global study thus far (only 15 patients enrolled in the everolimus group), there is no strong evidence to support the efficacy and safety of everolimus in Japanese patients. Moreover, the incidence of interstitial lung diseases (ILD) in the temsirolimus Asian phase-II study was significantly higher as compared to Western phase-III data. Therefore, it is very important to establish the AE profile of everolimus in the Japanese population. Methods: The target patient population consisted of patients with advanced renal cell carcinoma who had been treated with everolimus since January 2010. Data on efficacy, PFS and response rate and safety were collected and demographic factors that could be correlated with efficacy and safety were carefully investigated. Data will be up-dated until May 2011, when the final data from approximately 150 cases will be shown. Results: Demographic data from 87 evaluable patients is as follows: mean age of 62 years; male to female ratio of 78:22; PS of 0 in 73%, 1 in 14%, 2-4 in 13%; histological diagnosis of clear cell carcinoma in 79%. Prior treatments were cytokines in 52%, sunitinib in 72%, and sorafenib in 60%. The reasons for discontinuation of prior therapy were progression (73%), adverse events (25%), and others (2%). Efficacy was demonstrated with a median PFS of 2.8 months and RR of PR7%/SD47%/PD20%. The incidence of adverse events (all grades) was 85% and discontinuation due to AEs was 30 %. Major AEs were stomatitis (45%), thrombocytopenia (25%), and anemia (24%).Serious adverse events (Grades 3-4) were anemia (9%), thrombocytopenia (6%), hyperglycemia (5%), and ILD (5%). Onset of adverse events was less than 28 days after starting the administration of everolimus. Conclusions: These findings suggest that everolimus was shown to be associated with relatively serious adverse events in Japanese patients and further up-date is necessary to provide an Asian AE profile of everolimus.

Epidemiology of interstitial lung diseases in Greece

Few data are available on the epidemiology of interstitial lung diseases (ILDs), especially after the current classification of idiopathic interstitial pneumonias. The aim of this study is to provide data on the epidemiology of ILDs in Greece, under the ATS/ERS international consensus. Departments of Pneumonology were contacted and asked to complete a questionnaire for every case of ILD that was alive on 2004 as well as for every new case from 1st January 2004 to 31st December 2004. Questions on the patients' demographic data, the exact diagnosis and the procedures used to establish the diagnosis were included. Centers covering about 60% of the Greek population have been analyzed. A total of 967 cases have been registered. The estimated prevalence of ILDs is 17.3 cases per 100,000 inhabitants. The estimated annual incidence of ILDs is 4.63 new cases per 100,000 inhabitants. The most frequent disease is sarcoidosis (34.1%), followed in decreasing order by idiopathic pulmonary fibrosis (19.5%), ILD associated with collagen vascular diseases (12.4%), cryptogenic organizing pneumonia (5.3%), histiocytosis (3.8%), and hypersensitivity pneumonitis (2.6%). Unclassified ILD or not otherwise specified accounted for the 8.5% of prevalent cases. These data suggest that sarcoidosis and idiopathic pulmonary fibrosis are the most frequent ILDs in our population. In comparison with the few previous reports, interesting dissimilarities have been observed.

The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study

BackgroundCurrent data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.MethodsAll persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.ResultsA total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".ConclusionThe incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive.

Low expressions of surfactant-associated protein (SP-A) in cancer tissues or in normal bronchial epithelial cells by immuno-histochemistry predict interstitial lung diseases (ILDs) induced by gefitinib in patients with advanced non-small cell lung cancer (NSCLC)

7188 Background: Gefitinib, an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for patients with non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) induced by gefitinib has been reported as a severe adverse effect, and the incidence of the ILD is likely much higher in Asia than in western countries. We have previously reported that frequency and mortality rate of ILD in Japan were 3.5% and 1.6%, respectively (Proc. Am. Soc. Clin. Oncol. 23, Abs.7064, 2004.) Although, predictive clinical backgrounds of ILD by multivariate analysis were male, current/former smoker or hypoxia before the treatment of gefitinib, biological predictive marker is little known. EGF stimulates surfactant-associated protein A (SP-A) synthesis in fetal lung tissue through ligand binding to EGFR. Tyrosine kinase inhibitor or anti-sense against EGFR decreases expression of SP-A in vivo, or in vitro. Methods: We determined SP-A protein expression levels in cancer tissues or in normal bronchial epithelial cells by immuno-histochemistry using a specific antibody in paraffin embedded specimens from NSCLC patients before the treatment of gefitinib. We have retrospectively reviewed each 10 patients who have incidence of ILD or no incidence of ILD, receiving equally gefitinib at a dose of 250 mg once daily. Results: SP-A expression in cancer tissues was not detectable in Pt with ILD (0/10) in contrast with 50% (5/10. All five have above +2 exp. Level.) in Pt with non-ILD (p<0.05). SP-A expression in normal bronchial epithelial cells was 20% reactive (2/10. Both have +1 exp. Level.) in Pt with ILD, on the other hand, 80% (8/10). in Pt with non-ILD (p<0.05). Thus, low expressions of SP-A were associated with the incidence of ILD induced by gefitinib. EGFR expression in tumor or normal alveolar epithelium was not correlated with incidence of ILD. Conclusions: SP-A expression levels in cancer tissue or in normal bronchial cell before the treatment of gefitinib are potent biomarkers to predict ILD. No significant financial relationships to disclose.

Interstitial lung diseases (ILD) induced by gefitinib in patients with advanced non-small cell lung cancer (NSCLC): Results of a West Japan Thoracic Oncology Group (WJTOG) epidemiological survey

7064 Background: Gefitinib was approved by the regulatory of Japanese Ministry, first in the world, on July 5, 2002. From Aug to Dec in 2002, more than 19,000 patients with NSCLC took gefitinib in Japan. It had seemed unlikely that gefitinib had lethal toxicity. However, 358 patients (approximately 1.9%) suffered from ILD, and 114 (approximately 0.6%) of them had been dead by Dec 13, 2002, according to the report from AstraZeneca. The high incidence and fatality of ILD became a serious social issue in Japan. To clarify the incidence of ILD induced by gefitinib, and to identify the risk factors related to ILD developing, we conducted a retrospective survey. Methods: Questionnaires were delivered to 112 affiliated institutions of WJTOG, which asked for patient's characteristics and their clinical information accompanied with treatment of gefitinib from Aug 31 to Dec 31 in 2002 in detail. Results: Eighty-four (75%) institutions replied with information containing a total of 1,976 patients. ILD occurred in 64 patients (3.2%, 95%CI: 2.5–4.1%), which was diagnosed by five experts for thoracic radiology in the extramurally reviews, and 25 (1.3%, 95%CI: 0.8–1.9%) had died. We analyzed the risk factors of ILD to compare 63 patients developing ILD with 1,661 patients as a control. Multivariate analysis indicated that the predictive risk factors of ILD developing were male (odds ratio: 4.35), smoker (4.76), and existence of idiopathic pulmonary fibrosis (IPF) (2.77). We also analyzed the predictive factors for response on our constructing database. The response rate was 20.4% of 1,724 patients treated gefitinib, although we did not evaluate it extramurally. Furthermore, we are going to evaluate survival for patients treated with gefitinib at the meeting. Conclusions: The highly risk group for developing ILD induced by gefitinib was identified clinically. Patients with NSCLC must be treated with gefitinib considering the risk and clinical benefit ratio. Further translational studies are needed to clarify the risk and benefit related to gefitinib on genomics and proteomics. No significant financial relationships to disclose.

Incidence of interstitial lung diseases in the south of Spain 1998-2000: the RENIA study.

This study aims to describe the distribution of interstitial lung diseases (ILD) in the South of Spain. A prospective multicentre population-based registry was established in nine provinces in the south of Spain with a population of 6,848,243 during a 3-year period (1998-2000). The number of participant physicians was 36 among 29 public hospitals. The number of diagnoses recorded was 66, divided in eight categories and coded according to ICD-9. A consensus document was elaborated for the classification of diseases and their diagnostic criteria. The number of cases declared was analysed each 3 months and communicated to each one of the participants. There were 744 cases of them registered with an annual incidence of 3.62 cases/ 100,000. 40.1% of diagnoses were biopsy confirmed. Men had a slightly higher incidence (4.18 cases/ 100,000/year) than women (3.07 cases/100,000/year). The most frequent diseases found were: idiopathic interstitial pneumonias (38.58%), ILD associated to systemic diseases (20.97%), and Sarcoidosis (11.69%). According to province distribution, most of the cases were grouped in an area between the provinces of Seville and Cordoba, which comprised more than 50% of cases. The study of the incidence of ILD depicts an intermediate situation from previous studies on the incidence and distribution of this group of diseases.

REGISTRATION OF INTERSTITIAL LUNG DISEASES BY 20 CENTRES OF RESPIRATORY MEDICINE IN FLANDERS

We report the results of a prospective registration of the prevalence of interstitial lung diseases by 20 centres of respiratory medicine in Flanders from January 1992 till July 1996. The 20 centres registered a total of 362 cases. Sarcoidosis (31% with inclusion of stage I, or 22% without stage I), idiopathic pulmonary fibrosis (20%), hypersensitivity pneumonitis (13%) and unclassified forms of interstitial lung diseases (9%) were the most often diagnosed diseases. The mean age of the patients was 52 ± 17 (SD) years, but ranged from 32 ± 10 years in histiocytosis X to 70 ± 13 years in drug induced interstitial lung diseases. The male to female ratio was 1.3 but ranged from 2.3 in interstitial lung diseases due to inhalation of inorganic materials to 0.8 in interstitial lung diseases due to connective tissue disease. The diagnosis was considered certain in 60%, probable in 30% and possible in 10%. In 50% of the cases the diagnosis was proven by biopsy and the most often used biopsy technique was transbronchiolo-alveolar biopsy (40% of biopsies) followed by open lung biopsy (32%). At diagnosis vital capacity was 82±22% pred. (ranging from 92±19% in sarcoidosis to 71±24% in idiopathic pulmonary fibrosis) and CO-diffusing capacity was 77±19% pred. (ranging from 77±19% in sarcoidosis to 41±13% in drug induced pneumonitis). The regional frequency of interstitial lung diseases in Flanders varied widely and was not proportional to the regional distribution of the 20 contributing centres. In conclusion this registration provides interesting information on the occurrence and presentation of the different forms of interstitial lung diseases, although it may still underestimate the real prevalence and incidence of interstitial lung diseases.