Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal

Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and β-catenin in developing human lung tissues from 12 to 40 weeks of gestation.</p> <p>Methods</p> <p>Fortyseven cases of developing human lung including pseudoglandular, canalicular, saccular and alveolar periods were analyzed by immunohistochemisty for E- and N-cadherin and β-catenin and twentyone cases were also investigated by RT-PCR for E- and N-cadherin and β-catenin. For identifying the lung cells, the sections were also stained with antibodies against thyroid transcription factor-1 (TTF-1) and caveolin-1. Normal adult lung tissue was used as a control.</p> <p>E-cadherin was strongly expressed in epithelium of bronchi and large bronchioles from week 12 onwards and it was also positive in alveoli in pretype II cells and type II cells. N-cadherin was present in most of the epithelial cells of bronchi and the largest bronchioles during the pseudo-glandular and canalicular periods. N-cadherin was not detected in epithelium of developing alveoli. β-catenin was strongly membrane-bound and positively expressed in bronchial epithelium from week 12 to week 40; it showed nuclear positivity in both developing airway epithelium and in the cells underneath the epithelium during pseudo-glandular period and to a lesser degree also in the canalicular period. β-catenin was positive in pretype II cells as well as in type I and type II pneumocytes within alveoli.</p> <p>RT-PCR analyses revealed detectable amounts of RNAs of E- and N-cadherin and β-catenin in all cases studied. The amounts of RNAs were higher in early stages of gestation.</p> <p>Conclusions</p> <p>E-cadherin is widely expressed in bronchial and alveolar epithelial cells. N-cadherin exhibit extensive epithelial positivity in bronchial epithelial cells during early lung development. The presence of β-catenin was observed in several cell types with a distinct location in tissue and cells in various gestational stages, indicating that it possesses several roles during lung development. The expressions of protein and mRNAs of E- and N-cadherin and β-catenin were higher in early gestation compared to of the end. Moreover, the expressions of these factors were higher during the lung development than in the adult human lung.</p

Are physicians in primary health care able to recognize pulmonary fibrosis?

Background: The early diagnosis of idiopathic pulmonary fibrosis (IPF) has become increasingly important due to evolving treatment options. IPF patients experience a significant delay in receiving an accurate diagnosis, thus delayed access to tertiary care is associated with higher mortality independently from disease severity. Objective: The aims were to evaluate whether there had been a delay in the referral process, and to determine whether the referring doctors had suspected IPF or other interstitial lung disease (ILD) already during the time of referral. Methods: Ninety-five referral letters of patients with IPF identified from the FinnishIPF registry were evaluated with respect to time of referral, referring unit, grounds for referral, symptoms, smoking status, occupational history, clinical examinations, co-morbidities, medication, radiological findings and lung function. Results: Fifty-nine percent of referral letters originated from primary public health care. The time from symptom onset to referral was reported in 60% of cases, mean time being 1.5 (0.8-2.3) (95% CI) years. The main reason for referral was a suspicion of interstitial lung disease (ILD) (63%); changes in chest X-ray were one reason for referring in 53% of cases. Lung auscultation was reported in 70% and inspiratory crackles in 52% of referral letters. Conclusions: Primary care doctors suspected lung fibrosis early in the course of disease. Lung auscultation and chest X-rays were the most common investigational abnormalities in the referrals. Providing general practitioners with more information of ILDs might shorten the delay from symptom onset to referral.Peer reviewe

National data on prevalence of idiopathic pulmonary fibrosis and antifibrotic drug use in Finnish specialised care

Introduction The previous data concerning the prevalence of idiopathic pulmonary fibrosis (IPF) and the frequency of antifibrotic drug use in Finland were based on research registries and medical records whereas nationwide data on the number of patients with IPF in specialised care and those on antifibrotic treatment have not been published. Methods We made an information request to the Finnish National Hospital Discharge Register (Hilmo) covering the whole population of Finland to find out the annual numbers of patients with IPF treated in specialised care in 2016-2021. The numbers of the patients initiating and using pirfenidone and nintedanib were requested from the Social Insurance Institution of Finland (Kela) for the same time period. Results The estimated prevalence of IPF in specialised care was 36.0 per 100 000 in 2021, having increased since 2016. The number of antifibrotic drug users and their proportion of outpatients with IPF had also risen during the follow-up period. In 2021, 35% of the patients with IPF used pirfenidone or nintedanib. The number of inpatients treated in specialised care because of IPF had declined during 2016-2021. Conclusions The prevalence of IPF was higher than expected in Finnish specialised care and had increased during the 6-year follow-up time. The increase in the number of patients with IPF using antifibrotic drugs might have diminished the need for IPF-related hospitalisations.Peer reviewe

Tuleeko toisiolaista tutkimuksen tulppa vai kasvumoottori?

Rekisteritietojen yhdistäminen ei ole vain tekninen ongelma, vaan edellyttää myös sisällön yhteismitallisuutta. Paras kliinisen ¬informatiikan osaaminen on yliopistosairaaloissa. Sitä ei pidä heittää hukkaan

Demographics and survival of patients with idiopathic pulmonary fibrosis in the FinnishIPF registry

Peer reviewe

Delay and inequalities in the treatment of idiopathic pulmonary fibrosis : the case of two Nordic countries

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011-2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries. Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study. Data on demographics and lung function at the time of inclusion were collected. Access to antifibrotic drugs and data on disease outcomes, mortality and the proportion of patients who underwent lung transplantation, was collected during a 3-year follow up. Results: One-hundred and fifty-two patients from the Finnish and 160 patients from the Swedish IPF-cohorts were included in the study. At inclusion, Finnish patients were significantly older than the Swedish patients (74.6 years vs 72.5 years, p = 0.017). The proportion of non-smokers was significantly higher in the Finnish cohort (41.7% vs 26.9%, p = 0.007). Forced vital capacity (FVC), % of predicted (78.2 vs 71.7 for Finnish and Swedish patients, respectively, p = 0.01) and diffusion capacity for carbon monoxide (DLCO), % of predicted (53.3 vs 48.2 for Finnish and Swedish patients, respectively, p = 0.002) were significantly higher in the Finnish cohort compared to the Swedish cohort at the time of inclusion. During the 3-year follow up period, 45 (29.6%) Finnish and 111 (69.4%) Swedish patients, respectively, were initiated on treatment with an antifibrotic drug (pirfenidone or nintedanib) (p <0.001). When comparing possible determinants of treatment, patients with higher FVC % were less likely to start antifibrotic drugs (OR 0.96, 95% CI 0.93-1.00, p <0.024). To be resident in Sweden was the main determinant for receiving antifibrotic drugs (OR 5.48, 95% CI 2.65-11.33, p <0.0001). No significant difference in number of deaths and lung transplantation during the follow up period was found. Conclusions: This study highlights differences concerning how IPF patients are treated in Finland and Sweden. How these differences will influence the long-term outcome of these patients is unknown.Peer reviewe