Digital Care Pathway for Patients With Sleep Apnea in Specialized Care: Mixed Methods Study.

BACKGROUND: Sleep apnea is a significant public health disorder in Finland, with a prevalence of 3.7%. Continuous positive airway pressure (CPAP) therapy is the first-line treatment for moderate or severe sleep apnea. From November 18, 2019, all patients who started their CPAP therapy at Oulu University Hospital were attached to a sleep apnea digital care pathway (SA-DCP) and were instructed on its use. Some patients still did not use the SA-DCP although they had started their CPAP therapy. OBJECTIVE: We aimed to study health care professionals' (HCPs') perspectives on the SA-DCP and its usefulness for their work; whether the main targets of SA-DCP can be reached: shortening the initial guiding sessions of CPAP therapy, reducing patient calls and contact with HCPs, and improving patients' adherence to CPAP therapy; and patients' perspectives on the SA-DCP and its usefulness to them. METHODS: Overall, 6 HCPs were interviewed in May and June 2021. The survey for SA-DCP users (58/91, 64%) and SA-DCP nonusers (33/91, 36%) was conducted in 2 phases: from May to August 2021 and January to June 2022. CPAP device remote monitoring data were collected from SA-DCP users (80/170, 47.1%) and SA-DCP nonusers (90/170, 52.9%) in May 2021. The registered phone call data were collected during 2019, 2020, and 2021. Feedback on the SA-DCP was collected from 446 patients between February and March 2022. RESULTS: According to HCPs, introducing the SA-DCP had not yet significantly improved their workload and work practices, but it had brought more flexibility in some communication situations. A larger proportion of SA-DCP users familiarized themselves with prior information about CPAP therapy before the initial guiding session than nonusers (43/58, 74% vs 16/33, 49%; P=.02). Some patients still had not received prior information about CPAP therapy; therefore, most of the sessions were carried out according to their needs. According to the patient survey and remote monitoring data of CPAP devices, adherence to CPAP therapy was high for both SA-DCP users and nonusers. The number of patients' phone calls to HCPs did not decrease during the study. SA-DCP users perceived their abilities to use information and communications technology to be better than nonusers (mean 4.2, SD 0.8 vs mean 3.2, SD 1.2; P<.001). CONCLUSIONS: According to this study, not all the goals set for the introduction of the SA-DCP have been achieved. Despite using the SA-DCP, some patients still wanted to communicate with HCPs by phone. The most significant factors explaining the nonuse of the SA-DCP were lower digital literacy and older age of the patients. In the future, more attention should be paid to these user groups when designing and introducing upcoming digital care pathways.

Peer reviewers' willingness to review, their recommendations and quality of reviews after the Finnish Medical Journal switched from single-blind to double-blind peer review.

BACKGROUND: There is a power imbalance between authors and reviewers in single-blind peer review. We explored how switching from single-blind to double-blind peer review affected 1) the willingness of experts to review, 2) their publication recommendations, and 3) the quality of review reports. METHODS: The Finnish Medical Journal switched from single-blind to double-blind peer review in September 2017. The proportion of review invitations that resulted in a received review report was counted. The reviewers' recommendations of "accept as is", "minor revision", "major revision" or "reject" were explored. The content of the reviews was assessed by two experienced reviewers using the Review Quality Instrument modified to apply to both original research and review manuscripts. The study material comprised reviews submitted from September 2017 to February 2018. The controls were the reviews submitted between September 2015 and February 2016 and between September 2016 and February 2017. The reviewers' recommendations and the scorings of quality assessments were tested with the Chi square test, and the means of quality assessments with the independent-samples t test. RESULTS: A total of 118 double-blind first-round reviews of 59 manuscripts were compared with 232 single-blind first-round reviews of 116 manuscripts. The proportion of successful review invitations when reviewing single-blinded was 67%, and when reviewing double-blinded, 66%. When reviewing double-blinded, the reviewers recommended accept as is or minor revision less often than during the control period (59% vs. 73%), and major revision or rejection more often (41% vs 27%, P = 0.010). For the quality assessment, 116 reviews from the double-blind period were compared with 104 reviews conducted between September 2016 and February 2017. On a 1-5 scale (1 poor, 5 excellent), double-blind reviews received higher overall proportion of ratings of 4 and 5 than single-blind reviews (56% vs. 49%, P < 0.001). Means for the overall quality of double-blind reviews were 3.38 (IQR, 3.33-3.44) vs. 3.22 (3.17-3.28; P < 0.001) for single-blind reviews. CONCLUSIONS: The quality of the reviews conducted double-blind was better than of those conducted single-blind. Switching to double-blind review did not alter the reviewers' willingness to review. The reviewers became slightly more critical.

Long-Term Results of Pediatric Congenital Pulmonary Malformation: A Population-Based Matched Case-Control Study with a Mean 7-Year Follow-Up.

Symptomatic congenital pulmonary malformations (CPMs) are a group of anomalies involving the lungs. The long-term outcomes of these patients are not well known. The present research aimed to study the pulmonary function, respiratory morbidity, and health-related quality of life (QoL) of patients treated for CPMs. All children (<16 years of age) treated for CPMs in 2002−2012 (in Oulu University Hospital) were invited to the follow-up visit. Altogether, there were 22 patients, out of which 17 (77%) participated. The mean follow-up time was 6.6 (ranged from 3 to 16) years. Pulmonary function tests, diffusing capacity, respiratory morbidity, and QoL were determined as the primary outcomes. Potential residual malformations and lung anatomy were investigated using computer tomography (CT) imaging. The outcomes were compared to the age- and sex-matched healthy controls. The forced expiratory volume at 1 s (FEV1, Z-score) remained lower in operated patients compared to the healthy controls (−1.57 ± SD 1.35 vs. −0.39 ± SD −0.86, p-value 0.005). There were no differences in respiratory morbidity or QoL between the patients and the controls. The surgical approach (lobectomy vs. partial resection) did not affect lung function. A younger age (<1 year of age) at the time of the surgery seemed to result in a higher lung capacity, but the finding was not statistically significant. Patients with CPMs treated with surgery were satisfied with their wellbeing in the long-term. A lower lung function did not have an impact on their wellbeing. However, there was a slight decrease in lung function compared to the healthy controls, and a clinical follow-up of the patients was recommended.

Maternal smoking trajectory during pregnancy predicts offspring's smoking and substance use - The Northern Finland birth cohort 1966 study.

The aim was to characterize the association of maternal smoking trajectory during pregnancy with offspring's smoking, alcohol and substance use behavior. We used the prospective Northern Finland Birth Cohort 1966 study including 11,653 mothers and their offspring followed up from mothers' mid-pregnancy to age of 46 years. Main exposure was number of smoked cigarettes per day at each month of pregnancy. Outcome measures were offspring's smoking, alcohol and drug use at age 14, starting age of smoking, ever-smoking, and smoked pack-years until age 46. Four maternal smoking trajectories during pregnancy were identified with latent class trajectory modelling, namely "non-smokers" (86.0% of mothers), "early quitters" (2.0%), "late quitters" (2.1%), and "consistent smokers" (9.9%). In comparison to non-smokers, all maternal smoking was associated with offspring's increased odds of lifetime smoking adjusted for sex of the child, father's smoking, occupational status and place of residence of family, marital status and mood of mother, and desirability of pregnancy. The consistent smoker's class was associated with offspring's number of smoked pack years by midlife (median [interquartile range]: 8.3 [1.4-17.4] vs. 4.8 [0.0-13.0], p = 0.028), and alcohol use in young age (odds ratio 1.23 [95% confidence interval 1.05-1.43]). Overall, to prevent parent-offspring transmission of smoking, the cessation support should target women planning pregnancy. Negative effects of maternal continuous smoking during pregnancy include all substance use and reach up to offspring's middle age.

Smoking effect on the ultrastructural properties of cultured lung myofibroblasts.

This study aimed at an ultrastructural characterization of myofibroblasts cultured from different compartments of lung from never-smokers and smokers with or without COPD. In addition, we evaluated the expression of alpha smooth muscle actin (α-SMA), a marker for myofibroblasts, and contractile properties. Stromal cells cultured from central and corresponding peripheral or only from peripheral lung of never-smokers, smokers without COPD and COPD patients were analyzed by transmission electron microscopy (TEM), immunoelectron microscopy (IEM), Western analysis and/or by collagen gel contraction assay. TEM revealed that myofibroblasts cultured from smokers and COPD had less prominent intracellular actin filaments. We also examined fibronexus (FNX), which is a typical ultrastructural feature of myofibroblasts, and observed that patients with COPD more frequently had tandem-like FNX as compared to other samples. Western analysis showed that the samples derived from the central lung of never-smokers expressed higher levels of α-SMA than those of smokers and COPD patients. Cells from central lung were less contractile than those from peripheral lung. We conclude that myofibroblasts have variable ultrastructural and functional properties based on their localization in the lung and, moreover, these properties are affected by both smoking history and COPD.

Lifelong smoking trajectories of Northern Finns are characterized by sociodemographic and lifestyle differences in a 46-year follow-up.

Smoking remains among the leading causes of mortality worldwide. Obtaining a comprehensive understanding of a population's smoking behaviour is essential for tobacco control. Here, we aim to characterize lifelong smoking patterns and explore underlying sociodemographic and lifestyle factors in a population-based birth cohort population followed up for 46 years. Our analysis is based on 5797 individuals from the Northern Finland Birth Cohort 1966 who self-reported their tobacco smoking behaviour at the ages of 14, 31 and 46. Data on sex, education, employment, body mass index, physical activity, alcohol consumption, and substance addiction were also collected at the follow-ups. We profile each individual's annual smoking history from the age of 5 to 47, and conduct a latent class trajectory analysis on the data. We then characterize the identified smoking trajectory classes in terms of the background variables, and compare the heaviest smokers with other classes in order to reveal specific predictors of non-smoking and discontinued smoking. Six smoking trajectories are identified in our sample: never-smokers (class size 41.0%), youth smokers (12.6%), young adult quitters (10.8%), late adult quitters (10.5%), late starters (4.3%), and lifetime smokers (20.7%). Smoking is generally associated with male sex, lower socioeconomic status and unhealthier lifestyle. Multivariable between-class comparisons identify unemployment (odds ratio [OR] 1.28-1.45) and physical inactivity (OR 1.20-1.52) as significant predictors of lifetime smoking relative to any other class. Female sex increases the odds of never-smoking and youth smoking (OR 1.29-1.33), and male sex increases the odds of adult quitting (OR 1.30-1.41), relative to lifetime smoking. We expect future initiatives to benefit from our data by exploiting the identified predictors as direct targets of intervention, or as a means of identifying individuals who may benefit from such interventions.

COPD Comorbidities Predict High Mortality - Asthma-COPD-Overlap Has Better Prognosis.

The purpose of this study was to investigate the characteristics and survival of patients with COPD and asthma-COPD overlap (ACO) and how these patient groups differ from each other. We examined the impact of different comorbidities, multimorbidity, lung function and other factors have on survival in COPD and ACO patients. We also examined the causes of death to determine how many patients die of other than respiratory diseases. This retrospective study includes 214 patients with an exacerbation of COPD requiring hospitalisation during the year of 2005. The patients were followed up until the end of year 2015. The survival of ACO patients was significantly higher than COPD patients (4.7 vs. 1.7 years, p = 0.001). Poor lung function predicted worse survival in both patient groups, but the prognosis was still better in ACO patients with both FEV1 over and under 50% of predicted (median survival 8.4 years vs. 5.8 years, p < 0.001) compared to COPD (4.9 and 3.1 years, respectively). In this study setting, the negative effect of having three or more comorbidities on survival was significant in both groups. We didn't see major differences in the profiles of comorbidity patterns, in the underlying cause of deaths or in the pulmonary functions between ACO and COPD groups at the beginning of follow-up. Patients with a BMI over 25 seemed to have a trend for better survival (p = 0.055), but no differences were found between ACO and COPD groups.

Pneumonic tularaemia: experience of 58 cases from 2000 to 2012 in Northern Finland.

BACKGROUND: Pneumonic tularaemia is less common clinical form of tularaemia compared with the ulceroglandular form, with only a limited number of case reports and case series in Europe. In Finland, Northern Ostrobothnia is an endemic area of tularaemia with occasional seasonal outbreaks. METHODS: In our study, a consecutive series of 58 pneumonic tularaemia cases diagnosed and treated in Oulu University Hospital in 2000-2012 were retrospectively analysed in terms of epidemiology, clinical course, and prognosis. RESULTS: The incidence of pneumonic tularaemia showed peaks in cycles of a few years and most cases were diagnosed in late summer or early autumn. Respiratory symptoms were absent in 47% of patients, and 7% had normal chest X-ray. The chest computed tomography (CT) was performed in 81% of patients, demonstrating variable findings associated with pneumonic tularaemia. Bronchoscopy was performed for 22 (38%) patients and four (18%) of these also proceeded into mediastinoscopy. Moreover, thoracoscopy was performed for one (2%) patient. Two (3%) patients were treated shortly in the intensive care unit (ICU) during their stay in hospital. No mortality was observed. CONCLUSIONS: Most cases of pneumonic tularaemia are diagnosed during the seasonal outbreaks. The lack of specific symptoms often complicates the diagnosis and leads to unnecessarily invasive examinations.

Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines.

The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers. The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations. The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient. The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS). These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions. For the low exacerbation risk phenotype, pharmacotherapy with short-acting ß2 -agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms. If short-acting bronchodilators are not enough to control symptoms, a long-acting ß2 -agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended. For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting ß2 -agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting ß2 -agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1  < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast. ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (ß2 -agonist or anticholinergic or both).

[Work aggravated asthma]. / Tyon pahentama astma.

One out of five working persons with asthma has work-related respiratory symptoms. When exploring the symptoms of a working-age patient it is essential to survey the job description and working conditions. Early intervention in the factors aggravating the respiratory symptoms will decrease morbidity, maintain working capacity and improve the quality of life. Occupational health service and the employer play a central role in identifying and decreasing the exposure factors in the working environment as well as in patient guidance for asthma therapy and protecting from the stimuli. The working capacity of an asthmatic person can be improved by applying vocational rehabilitation.

[Update on current care guideline: chronic obstructive pulmonary disease (COPD)]. / Keuhkoahtaumatauti.

Clinical serverity of COPD is based not only on the grade of obstruction in spirometry, but also on symptoms and risk of exacerbations. Symptoms can be defined by questionnaires, such as CAT-test (COPD assessment -test) or mMRC (modified Medical Research Council -test). Smoking cessation and physical activity are important treatment options. Pharmacological treatment is selected by symptoms, risk of exacerbations and co-occurrence of asthma and COPD. Non-invasive ventilation (NIV) is recommended in the treatment of severe hypercapnic exacerbations. Palliative treatment of end stage COPD is included in the guidelines.

Slug is associated with poor survival in squamous cell carcinoma of the lung.

We investigated the expression of slug in a large set of lung squamous and adenocarcinomas to determine common or dissimilar features in its expression in these two most common forms of lung cancer. To investigate slug related tumor spread we studied the expression of vimentin, claudin 1, MMP2 and MMP9 in these tumors and their relation to slug. Addition, cell invasion assays, mRNA analysis and zymographic tests were performed to study epitheliomesenchymal transition (EMT) related changes in slug blocked lung cell lines. According to the results slug expression did not significantly differ between squamous (SCC) and adenocarcinoma (AC) (P = 0.25). In SCC, slug associated with vimentin (P = 0.016). In AC, claudin 1 associated with MMP2 (P = 0.037). In SCC slug expression had a poor prognositic significance (P = 0.006) and it had independent prognostic value (P = 0.037). In AC MMP2 had a worsening impact on survival (P = 0.021) and it had independent prognostic value (P = 0.002). In cell invasion assays, slug knockdown inhibited the invasion and migration of BEAS-2B, SK-LU1 and SK-MES1 cell lines. The mRNA expression of claudin 1 was downregulated in SK-LU1 cell line. Both tumor cell lines expressed MMP2 and in SK-MES1 slug inhibited line MMP2 appeared to decrease. The results show that slug associated EMT is more pronounced in lung SCC than AC. Slug associated with vimentin in SCC and had an independent prognostic value in this tumor type. Forced slug inhibition might be one putative way of treatment of SCC of the lung.

Stromal cells can be cultured and characterized from diagnostic bronchoalveolar fluid samples obtained from patients with various types of interstitial lung diseases.

Increased proliferation of stromal cells is a typical feature encountered in several lung diseases. The objective of this study was to evaluate the success of standardized process for culturing stromal cells from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples collected from various patients and to characterize the cultured cells. Small volumes (average 15 mL) of BAL fluid samples were collected from 98 patients who underwent bronchoscopy and BAL for diagnostic purposes. The cells were cultured in vitro and characterized by immunohistochemistry, electron microscopy, flow cytometry and differentiation tests. Cells could be cultured from 62% of samples with the success rate varying with the disease (p = 0.003). Cultures from samples of the patients with idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, connective tissue disorder associated interstitial lung disease and allergic alveolitis had a higher success rate than samples derived from control lung (p < 0.001, 0.03, 0.03 and 0.044, respectively). Smokers had a higher success rate compared with non-smokers (p = 0.035). The cultured cells were fibroblasts or myofibroblasts, but shared also similarities with progenitor-type cells. The study shows that mesenchymal cells can be cultured and studied from small volumes of diagnostic BAL fluid samples from patients with several different types of lung diseases.

GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma.

GASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.

[Irritant-induced asthma]. / Ärsytyksen aiheuttama astma.

Irritant-induced asthma is a rare disease, usually being caused by an accidental or other exceptionally strong exposure to substances irritating the respiratory passages. High-dose inhaled corticosteroid medication is immediately started at the emergency call service. If severe exposure is suspected, it is important to monitor the patient at least for a couple of days in hospital. Immediately after the acute stage diagnostic investigations are carried out, including a metacholine or histamine challenge test, since demonstration of airway hyperreactivity is of diagnostic and prognostic significance. The asthma may remain permanent.

Myofibroblast expression in airways and alveoli is affected by smoking and COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD. METHODS: α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistochemical findings were correlated with clinical data. α-SMA protein was also analysed by Western blotting from fibroblastic cells cultured from peripheral lung of non-smokers, smokers without COPD and smokers with COPD. RESULTS: In many cases, the endings of the detached alveolar walls were widened, the structures of which were named as widened alveolar tips. Widened alveolar tips contained α-SMA positive cells, which were obviously myofibroblasts. There were less alveolar tips containing positive cells for α-SMA in alveoli and α-SMA positive cells in bronchioles in smokers and in COPD compared to non-smokers. The quantity of α-SMA positive cells was increased in bronchi in COPD. Tn-C was elevated in bronchi in COPD and smokers' lung. The α-SMA protein level was 1.43-fold higher in stromal cells cultured from non-smokers than in those of smokers. CONCLUSIONS: Myofibroblasts are localized variably in normal and diseased lung. This indicates that they have roles in both regeneration of lung and pathogenesis of COPD. The widened alveolar tips, these newly characterized histological structures, seemed to be the source of myofibroblasts at the alveolar level.

[Update on current care guidelines: asthma]. / Astma.

Asthma is an inflammatory disease of the lower airways. The typical symptoms of asthma are cough, wheezing and shortness of breath. Asthma is diagnosed based on measures of pulmonary function showing variable or reversible airways obstruction. The basic pharmacological treatment consists of alleviating the asthmatic inflammation with regular inhaled glucocorticoids and relieving sudden obstructions with as-needed inhaled beta2-agonists. The treatment is adjusted based on asthma control. If good control of asthma is not achieved with low to medium doses of inhaled glucocorticoids, additional control medication (inhaled long acting beta2-agonists, antileukotrienes, in adults also theophylline or tiotrohium) should be introduced.

Snail promotes an invasive phenotype in lung carcinoma.

BACKGROUND: Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). METHODS: To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines. RESULTS: Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree. CONCLUSIONS: The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree.

Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

Genotypic and phenotypic characterization of carriage and invasive disease isolates of Neisseria meningitidis in Finland.

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.