Characteristics of idiopathic pulmonary fibrosis -associated cough. a case-control study.

BACKGROUND: Most patients with idiopathic pulmonary fibrosis (IPF) complain of cough. IPF-associated cough is widely characterized as dry or non-productive. The aim of this study was to compare chronic cough in early stage IPF patients to cough in subjects with chronic cough from a community-based sample and, especially, to investigate whether cough in IPF is less productive than chronic cough in a community-based sample. METHODS: The IPF cough population consisted of 46 biopsy-confirmed patients who complained of chronic cough. Control population consisted of subjects with chronic cough, gathered by a community-based email survey sent to public service employees and the Finnish Pensioners' Federation. A case-control setting was applied by having four age, gender, and smoking-status matched subjects from the community sample for each IPF cough patient. A cough specific quality of life questionnaire (Leicester Cough Questionnaire (LCQ)) was filled in by all subjects. The LCQ questionnaire contains 19 questions, each question is scored from 1 to 7 and total score from 3 to 21 with a smaller value indicating more severe impairment. RESULTS: The sputum production frequency, as assessed by LCQ question 2, was 5.0 (3.0-6.0) in the IPF chronic cough population and 5.0 (3.0-6.0) in the community-based chronic cough population (median and interquartile range p= 0.72). The LCQ total score was 14.8 (11.5-18.1) in the IPF chronic cough population and 15.4 (13.0-17.5) in the community-based chronic cough population (p=0.76). The domain impact scores were physical, 4.9 (3.9-6.1) vs. 5.1 (4.5-5.6) (p=0.80); psychological, 4.6 (3.7-5.9) vs. 4.7 (3.9-5.7) (p=0.90); and social, 5.5 (3.7-6.5) vs. 5.5 (4.5-6.3) (p=0.84), respectively. Furthermore, cough response to paint or fumes, cough disturbing sleep, and cough frequency per day did not differ between the groups. CONCLUSION: Cough in early stage IPF patients was not distinguishable from chronic cough in the community-based population by LCQ. Especially, there was no difference in the self-reported frequency of cough-associated sputum production.

Inflammatory myositis-associated interstitial lung disease can be distinguished from that associated with other connective tissue diseases.

Background: Acute onset of interstitial lung disease (ILD) has been described in patients with idiopathic inflammatory myositis (IIM), but controlled studies about this issue are sparse. The aim of this study was to compare disease onset, demographics, and high-resolution computed tomography (HRCT) patterns in IIM-ILD and other connective tissue disease (CTD)-ILDs. Methods: Clinical and radiological data of 22 IIM-ILD and 132 other CTD-ILD patients was retrospectively gathered from hospital registries between January 2000 and November 2019. Data was re-assessed and compared using a multivariate analysis. Results: Compared to other CTD-ILDs, the patients with IIM-ILD were younger (59.7 vs. 68.0 years, P=0.023), more often non-smokers (71.4% vs. 45.7%, P=0.029) and displayed radiological nonspecific interstitial pneumonia/organizing pneumonia (NSIP/OP) overlap pattern more frequently (27.3% vs. 1.5%, P<0.001). The onset of ILD was acute with patients needing intensive care significantly more often in IIM-ILD than in other CTD-ILDs (22.7% vs. 2.3%, P<0.001). In most patients ILD was diagnosed before or simultaneously with IIM presentation unlike in other CTD-ILDs (90.9% vs. 47.7%, P<0.001). In multivariate analysis, NSIP/OP overlap pattern, acute onset disease treated in intensive care unit and ILD preceding or being diagnosed simultaneously with CTD were significantly associated with IIM-ILD. The multivariate model, supplemented with age, had excellent diagnostic performance identifying IIM-ILD [area under curve (AUC) 0.845]. Conclusions: Unlike other CTD-ILDs, IIM-ILD often develops acutely, simultaneously with the systemic disease. Therefore, clinicians should consider IIM-ILD as an option of differential diagnosis in patients with acute ILD and promptly test muscle enzymes as well as comprehensive autoantibody tests.

Virtual communication is commonly used in Finnish interstitial lung disease multidisciplinary meetings.

Multidisciplinary meeting (MDM) is a core element in the diagnosis of interstitial lung diseases (ILD). The aim of the study was to investigate the implementation and key elements related to ILD MDMs in Finnish specialized care, which is characterized by long travel distances and a large number of small centers treating patients suffering from ILDs. An electronic questionnaire was sent to ILD experts working at five academic centers of Finland regarding the implementation of ILD MDMs with the focus on utilization of virtual communication. Responses were received from all academic centers of Finland (n = 5) whose catchment areas cover all of Finland. ILD MDMs were organized in each center approximately every two weeks and the core participants included a radiologist, respiratory physicians, junior staff, pathologist and a rheumatologist. All non-academic centers could refer their patients to be evaluated in ILD MDM of an academic center. Virtual communication was utilized by all academic centers in the implementation of ILD MDMs, being most common among small centers located in Eastern and Northern Finland. Virtual access to ILD MDM of an academic center was available in most parts of Finland, enabling small centers to benefit from the ILD expertise of academic centers.

Comorbidities and Causes of Death of Patients With Asbestosis.

OBJECTIVE: Comorbidities are common and affect the prognosis of patients with interstitial lung diseases, but few previous studies have investigated patients with asbestosis. METHODS: We collected comorbidities and death causes of 116 patients with asbestosis treated in Oulu University Hospital. Causes of death were confirmed by autopsy in 68% of the cases. RESULTS: The most common comorbidities of asbestosis patients were pleural plaques (96%) and coronary artery disease (CAD; 67%). The prevalence of rheumatoid arthritis was 8.6%. The most common underlying causes of death were asbestosis (36%), CAD (24%), and lung cancer (LC) (10%). CAD and LC were associated with shorter survival in adjusted analyses. CONCLUSIONS: Patients with asbestosis have multiple comorbidities. Prevention and treatment of CAD and LC may influence the prognosis of asbestosis patients.

Reticulation pattern without honeycombing on high-resolution CT is associated with the risk of disease progression in interstitial lung diseases.

BACKGROUND: The disease course of idiopathic pulmonary fibrosis (IPF) is progressive and occasionally, other types of interstitial lung disease (ILD) may progress similarly to IPF. This study aimed to evaluate risk factors for disease progression within 24 months in patients with various ILDs. METHODS: This prospective study obtained 97 patients with a suspected ILD who underwent a transbronchial lung cryobiopsy. The extent of several high-resolution computed tomography (HRCT) patterns was assessed. Due to the inclusion criteria the study population presented a low extent of honeycombing and definite usual interstitial pneumonia (UIP) pattern on HRCT suggesting an early stage of ILD. Disease progression within 24 months despite treatment was defined as a relative decline of ≥ 10% in forced vital capacity (FVC), or a relative decline in FVC of ≥ 5% and one of the three additional criteria: (1) a decline in diffusion capacity to carbon monoxide (DLCO) ≥ 15%; (2) increased fibrosis on HRCT; (3) progressive symptoms, or progressive symptoms and increased fibrosis on HRCT. The same definition was utilized in patients with IPF and other ILDs. Risk factors for disease progression were evaluated in a multivariable logistic regression model. RESULTS: Disease progression was revealed in 52% of the patients with ILD, 51% of the patients with IPF, and 53% of the patients with other types of ILD. A high extent of reticulation on HRCT (Odds ratio [OR] 3.11, 95% Confidence interval [CI] 1.21-7.98, P = 0.019) and never smoking (OR 3.11, CI 1.12-8.63, P = 0.029) were associated with disease progression whereas platelet count (OR 2.06 per 100 units increase, CI 0.96-4.45, P = 0.065) did not quite reach statistical significance. CONCLUSION: Higher extent of reticulation on HRCT and never smoking appeared to associate with the risk of disease progression within 24 months in ILD patients without honeycombing. Approximately half of the patients with ILD revealed disease progression, and similar proportions were observed in patients with IPF and in other types of ILD.

Risk factors of clinically significant complications in transbronchial lung cryobiopsy: A prospective multi-center study.

BACKGROUND: The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients. METHODS: Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ≤90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications. RESULTS: The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03-1.65, p = 0.027) and young age (OR 7.96, CI 2.32-27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ≤30 days before the TBLC (OR 3.65, CI 0.911-14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10-16.0, p = 0.036). Procedure associated mortality ≤90 days was 1%. CONCLUSION: The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax.

Wintertime pharmacokinetics of intravenously and orally administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus).

OBJECTIVE: To investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus). STUDY DESIGN: A crossover design with an 11 day washout period. ANIMALS: A total of eight young male reindeer, aged 1.5-2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation. METHODS: The reindeer were administered meloxicam (0.5 mg kg-1 IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed. RESULTS: The pharmacokinetic values, median (range), were determined. Elimination half-life (t½) with the IV route (n = 4) was 15.2 (13.2-16.8) hours, the volume of distribution at steady state was 133 (113-151) mL kg-1 and clearance was 3.98 (2.63-5.29) mL hour-1 kg-1. After oral administration (n = 7), the peak plasma concentration (Cmax) was detected at 6 hours, t½ was 19.3 (16.7-20.5) hours, Cmax 1.82 (1.17-2.78) µg mL-1 and bioavailability (n = 3) 49 (46-73)%. No evident adverse effects were detected after either administration route. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of meloxicam (0.5 mg kg-1 IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma.

Utility of Cough Provocation Tests in Chronic Cough and Respiratory Diseases: A Comprehensive Review and Introduction of New Reference Ranges for the Capsaicin Test.

Cough provocation tests (CPTs) are an objective measurement of the sensitivity of the cough reflex arc. However, they are not established in clinical practice because a large variability of response in healthy subjects limits their diagnostic value. There is a paucity of studies that have investigated CPT reference ranges in healthy subjects. This systematic review describes the variability of the responses to CPTs in healthy subjects and factors that influence it. A new analysis of 134 healthy subjects was conducted to create reference ranges for single-breath capsaicin CPT by calculating the interquartile ranges for the provocative concentration of capsaicin to induce 2 and 5 coughs. Female subjects had a more sensitive cough reflex than male counterparts. The ability of CPTs to distinguish various respiratory diseases from healthy subjects was also reviewed. Cough sensitivity was consistently heightened in the following groups: unselected patients with chronic, refractory, or recurrent cough, unexplained chronic cough, gastro-esophageal reflux-associated cough, cough-variant asthma, lower airway symptoms induced by chemical irritants, and fibrotic interstitial lung diseases. In the following groups, hypersensitivity of the cough reflex was present in those individuals whose symptom profile was predominated by cough: asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and sarcoidosis. In the following conditions, patients usually cough in order to expectorate mucus from their airways, not because of a hypersensitive cough reflex arc: productive cough, asthma, upper airway cough syndrome, COPD, bronchiectasis, cystic fibrosis, and chronic respiratory infections. CPTs have the potential to identify patients with chronic respiratory symptoms due to cough reflex hypersensitivity, thereby providing a targeted approach for therapy.

Deep Inspiration-Provoked Cough: A Sign of Cough Reflex Arc Hypersensitivity.

Deep inspiration-provoked cough (DIPC) is a form of allotussia. Allotussia is thought to be a manifestation of cough reflex arc hypersensitivity but objective evidence about this is lacking. 36 subjects with chronic cough and 25 healthy subjects underwent mannitol and citric acid cough provocation tests. DIPC was defined as two or more coughs after deep inhalation of an empty mannitol capsule. Citric acid was administered utilizing a dosimetric nebulizer during controlled tidal breathing. Nine subjects demonstrated DIPC, 8/36 subjects with chronic cough and 1/25 healthy subjects (p = 0.048). The concentration of citric acid to provoke five or more coughs (C5) was 23.4 (63.8) mM among subjects with DIPC and 750 (2941) mM among the subjects without it (p = 0.006). The number of deep inspiration-provoked coughs correlated with the citric acid C5 (Rs -0.38, p = 0.002). In conclusion, DIPC, a form of allotussia, is associated with cough reflex arc hypersensitivity.Trial Registration Number.ClinicalTrials.gov database KUH5801136.

Cough-provocation tests with hypertonic aerosols.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

Comparison of disease progression subgroups in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia with an unpredictable course. The aims of this study were to retrospectively re-evaluate a cohort of patients with IPF according to the 2011 international IPF guidelines and 1) to characterize the subgroups of patients when classified according to their observed survival times and 2) to evaluate whether Composite Physiologic Index (CPI), Gender-Age-Physiology (GAP) Index or clinical variables could predict mortality. METHODS: Retrospective data was collected and patients were classified into subgroups according to their observed lifespans. Differences in clinical variables, CPI and GAP stages as well as in comorbidities were investigated between the subgroups. Predictors of mortality were identified by COX proportional hazard analyses. RESULTS: A total of 132 patients were included in this study. The disease course was rapid (≤ 2 years) in 30.0%, moderate (2-5 years) in 28.0% and slow (≥ 5 years) in 29.0% of the patients. Pulmonary function tests (PFT) and CPI at baseline differentiated significantly between the rapid disease course group and those patients with longer survival times. However, the predictive accuracy of the investigated clinical variables was mainly less than 0.80. The proportions of patients with comorbidities did not differ between the subgroups, but more patients with a rapid disease course were diagnosed with heart failure after the diagnosis of IPF. Most patients with a rapid disease course were categorized in GAP stages I and II, but all patients in GAP stage III had a rapid disease course. The best predictive multivariable model included age, gender and CPI. GAP staging had slightly better accuracy (0.67) than CPI (0.64) in predicting 2-year mortality. CONCLUSIONS: Although the patients with a rapid disease course could be differentiated at baseline in terms of PFT and CPI, the predictive accuracy of any single clinical variable as well as CPI and GAP remained low. GAP staging was unable to identify the majority of patients with a rapid disease progression. It is challenging to predict disease progression and mortality in IPF even with risk prediction models.

Comparison of mannitol and citric acid cough provocation tests.

RATIONALE: Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough provocation test, which has regulatory approval and can be performed utilizing a simple disposable inhaler in a standardized manner. OBJECTIVE: To compare the mannitol and citric acid cough provocation tests with respect to their ability to identify subjects with chronic cough and their tolerability. METHODS: Subjects with chronic cough (n = 36) and controls (n = 25) performed provocation tests with mannitol and citric acid. Both tests were video recorded. Cough sensitivity was expressed as coughs-to-dose ratios (CDR) and the cumulative doses to mannitol or concentration to citric acid evoking 5 coughs (C5). Forced expiratory volume in 1 s (FEV1), visual analogue scales (VAS), test completion rates and the total cough frequencies were analysed. RESULTS: Mannitol and citric acid CDR both effectively separated those with cough and the control subjects (AUC 0.847 and 0.803, respectively) as did C5 (AUC 0.823 and 0.763, respectively). There was a good correlation between the cough sensitivity provoked by the two stimuli, either expressed as CDR (r = 0.65, p < 0.001) or C5 (r = 0.53, p = 0.001). Both tests were similarly tolerated in terms of VAS, although more patients discontinued the mannitol test early, primarily due to cough. CONCLUSIONS: Mannitol and citric acid tests correlated well, equally identified subjects with chronic cough and their tolerability was similar. The feasibility issues, strict standardisation and regulatory approval may favour mannitol to be used in clinical cough research.

Underlying and immediate causes of death in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The most common cause of death of patients with idiopathic pulmonary fibrosis (IPF) has been reported to be the lung disease itself and mortality from IPF appears to be increasing. However, the causes of death in patients with IPF taking into account differences between genders and smoking histories as well as disease progression, have not been previously explored. METHODS: Retrospective data from hospital register and death certificates from national database of IPF patients treated in Kuopio University Hospital (KUH) from 2002 to 2012 were collected. Mortality was also explored from the death registry database via ICD-10 code J84 revealing the numbers of deaths from pulmonary fibrosis in Finland from 1998 to 2015. RESULTS: Out of 117 deaths, 26.5% were females and 73.5% males in KUH. The most common underlying causes of death were IPF 67.5% and ischemic heart diseases 14.8%. More males died for reasons other than IPF (39.5%) compared to females (12.9%) (p = 0.007). Pneumonia as the immediate cause of death was more common in males (27.9%) than in females (3.2%) (p = 0.004) and in ex-smokers (32.7%) compared to non-smokers (9.3%) (p = 0.007). Death register based mortality from pulmonary fibrosis is increasing in Finland. CONCLUSIONS: Even though the overall mortality was higher in males with IPF, the disease-specific mortality for IPF was higher in females i.e. in males, comorbidities were more often the underlying causes of death. Pneumonia-triggered acute exacerbations of IPF may be associated with smoking and gender since females and non-smokers were less likely to succumb to pneumonia. We conclude that disease progression at the end of life may vary depending on smoking habits and gender.

Several high-resolution computed tomography findings associate with survival and clinical features in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: To compare the presence and extent of several high-resolution computed tomography (HRCT) observations in different subtypes of rheumatoid arthritis-related interstitial lung disease (RA-ILD) and to examine associations between radiological findings, hospitalization, age, RA duration, pulmonary function tests (PFT) and survival. MATERIALS AND METHODS: HRCTs from 60 RA-ILD patients were independently evaluated and re-categorized into usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and unclassified subtypes by two radiologists. The presence and extent, which was reported using a semi-quantitative scoring system, of e.g. reticulation, ground-glass opacity, honeycombing, emphysema, traction bronchiectasis and architectural distortion were further evaluated and compared between the subtypes. Associations between radiological findings and survival were identified with the Kaplan-Meier method and Cox's univariate model. The correlations between radiological findings, hospitalization, age, pack years, RA duration and PFT were calculated using Spearman's correlation coefficient. RESULTS: The extents of reticulation (HR 1.144, p = 0.041), traction bronchiectasis (HR 1.184, p = 0.030), architectural distortion (HR 1.094, p = 0.044) and the presence of pleural fluid (HR 14.969, p < 0.001) were associated with decreased survival. A negative correlation was observed between ground-glass opacity (GGO) and the duration of RA (r = -0.308, p = 0.023). The extents of honeycombing (r = 0.266, p = 0.046), traction bronchiectasis (r = 0.333, p = 0.012) and architectural distortion (r = 0.353, p = 0.007) correlated with hospitalizations due to respiratory reasons. CONCLUSIONS: Many radiological findings associate with the course of the disease of RA-ILD and could potentially be useful when planning the RA treatment or evaluating the risk of death in these patients.

Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis.

BACKGROUND: Cigarette smoking has been associated with the risk of idiopathic pulmonary fibrosis (IPF). Certain comorbidities have been associated with reduced survival although some studies have indicated that current smokers have a longer survival than ex-smokers. Comorbidities in relation to smoking history have not been previously analyzed. METHODS: Retrospective data was collected and patients were categorized according to gender and smoking habits. Comorbidities and medications were collected. Predictive values for mortality were identified by COX proportional hazard analyses. RESULTS: We examined 45 non-smokers (53.3% female), 66 ex-smokers (9.1% female) and 17 current smokers (17.6% female) with IPF. Current smokers were younger at baseline (58.1 ± 8.74 years) compared to non-smokers (71.4 ± 8.74, p < 0.001) and ex-smokers (72.5 ±7.95, p <0.001). Median survival of non-smokers and current smokers was longer (55.0 and 52.0 months, respectively) than that of ex-smokers (36.0 months) (p=0.028 and 0.034, respectively). In age and severity adjusted analyses, smoking was not related to survival. Cardiovascular diseases (CVD) (72.7 %) were the most common comorbidities, current smokers had more chronic obstructive pulmonary disease (COPD) and lung cancer compared to ex-smokers (p<0.001). CVD, COPD and use of insulin were related to poorer survival in adjusted analyses. CONCLUSIONS: Smoking seems to influence the course of disease in IPF since current smokers developed the disease at a younger age in comparison to non-smokers and ex-smokers. No significant differences in the major comorbidities were detected between IPF patients with different smoking histories. The mechanism through which smoking influences IPF progression requires further investigation.

Are risk predicting models useful for estimating survival of patients with rheumatoid arthritis-associated interstitial lung disease?

BACKGROUND: Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients. METHODS: Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics. RESULTS: The median survival was 152 and 61 months in GAP / ILD-GAP stages I and II (p = 0.017). Both GAP and ILD-GAP models accurately estimated 1-year, 2-year and 3-year mortality. CPI (p = 0.025), GAP (p = 0.008) and ILD-GAP (p = 0.028) scores, age (p = 0.002), baseline diffusion capacity to carbon monoxide (DLCO) (p = 0.014) and hospitalization due to respiratory reasons (p = 0.039), were significant predictors of mortality in the univariate analysis, whereas forced vital capacity (FVC) was not predictive. CPI score (HR 1.03, p = 0.018) and baseline DLCO (HR 0.97, p = 0.011) remained significant predictors of mortality after adjusting for age. CONCLUSIONS: GAP and ILD-GAP are applicable for evaluating the risk of death of patients with RA-ILD in a similar manner as in those with IPF. Baseline DLCO and CPI score also predicted survival.

Variable course of disease of rheumatoid arthritis-associated usual interstitial pneumonia compared to other subtypes.

BACKGROUND: In rheumatoid arthritis-associated interstitial lung disease (RA-ILD), occurring in 10 % of patients with patients with RA, usual interstitial pattern (UIP) has shown to associate with poor prognosis but more detailed data about the course of the disease in different subtypes is limited. Our aim was to compare the disease course of patients with RA-ILD categorized into either UIP or other types of ILDs. METHODS: Clinical and radiological information of 59 patients with RA-ILD were re-assessed and re-classified into UIP or non-UIP groups, followed by a between-group comparison of demographic data, lung function, survival, cause of death and comorbidities. RESULTS: The majority of patients (n = 35/59.3 %) showed a radiological UIP-like pattern in high resolution computed tomography. The median survival was 92 months (95 % CI 62.8-121.2) in the UIP-group and 137 months (95 % CI 31.0-243.0) in the non-UIP-group (p = 0.417). Differences in course of disease were found in the number of hospitalizations for respiratory reasons (mean 1.9 ± 2.6 in UIP vs. 0.5 ± 0.9 in non-UIP group, p = 0.004), the use of oxygen therapy (8/22.9 % UIP patients vs. 0 non-UIP patients, p = 0.016), number of deaths (23/65.7 % vs. 10/41.7 %, p = 0.046) and decline in diffusion capacity (56 ± 20.6 vs. 69 ± 20.2, p = 0.021). Dyspnea and inspiratory crackles were detected more often in the UIP group. RA-ILD was the most common primary cause of death (39.4 % of cases). Hypertension, coronary artery disease, chronic obstructive pulmonary disease, heart insufficiency, diabetes and asthma were common comorbidities. ILD preceded RA diagnosis in 13.6 % of patients. CONCLUSIONS: The course of the disease in RA-UIP patients is different from the other RA-ILD subtypes. Several comorbidities associated commonly with RA-ILD, although ILD was the predominant primary cause of death.

Association of LOXL1 gene with Finnish exfoliation syndrome patients.

In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) gene associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) were investigated in the Finnish population. A case-control study of 59 sporadic patients with XFS, 82 with XFG, 71 with primary open-angle glaucoma (POAG) and 26 individuals without these disorders from the southern Finnish population, and a family study of an extended family with 28 patients with XFS or XFG and 92 unaffected relatives from Kökar islands, Southwestern Finnish archipelago, were conducted. Anonymous blood donors (n=404) were studied as population-based controls. Three SNPs, rs1048661 (R141L), rs3825942 (G153D) and rs2165241, of the LOXL1 gene were genotyped by PCR sequencing. Association and linkage analyses were carried out. In both case-control and family materials, significant association for allele G of rs1048661 (P=2.65 x 10(-5); P=0.0007), allele G of rs3825942 (P=2.24 x 10(-8); P=0.49) and allele T of rs2165241 (P=2.62 x 10(-13); P<0.0001) was found in XFS/XFG. However, linkage was not observed for LOXL1 risk alleles. The corresponding three-locus haplotype GGT increased the risk of XFS/ XFG nearly 15-fold relative to low-risk haplotype GAC (odds ratio (OR): 14.9, P=1.6 x 10(-16)). In conclusion, the earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population.

Prevalence of lactase persistent/non-persistent genotypes and milk consumption in a young population in north-west Russia.

AIM: To estimate the prevalence of the lactase non-persistent genotype (C/C-13910) in a northern Russian population in accordance with ethnicity, and to evaluate self-reported milk consumption depending on lactase activity. METHODS: Blood samples for genotyping lactase activity, defining the C/T-13910 variant by polymerase chain reaction, and direct sequencing were taken from 231 medical students of Russian origin aged 17-26 years. We analyzed milk product consumption by questionnaire which was specially designed for the estimation of milk consumption and abdominal complaints. RESULTS: We found that the prevalence of the C/C-13190 genotype in the northern Russian population was 35.6%. The other genotypes nearby C/T-13910 and associated with lactase activity were not present in the study population. The consumption of milk among people with the non-persistent genotype tended to be lower than among the lactose tolerant subjects, but was not statistically significant. CONCLUSION: An investigation of the lactase persistent genotype in a northern Russian population has not been performed before. The genotype did not affect the consumption of milk products in this population which could be explained by low consumption of milk products among the entire study population.