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Background: Interstitial lung diseases (ILD) include a wide range of diseases impacting lung parenchyma and leading to fibrosis and architectural distortion. Chronic cough and dyspnea are common symptoms which affect the quality of life (QoL) in ILD patients. The mechanisms of cough in ILD patients are still unknown. The aim of this study was to prospectively investigate histological, radiological, and physiological determinants of cough-related QoL in ILD patients who underwent transbronchial lung cryobiopsy (TBLC)., Methods: All patients (n = 111) filled in The Leicester Cough Questionnaire (LCQ) and The St George's Respiratory Questionnaire (SGRQ). They underwent lung function tests, forced vital capacity (FVC), forced vital expiratory volume in 1 s (FEV1), diffusion capacity to carbon monoxide (DLCO), high-resolution computed tomography (HRCT), and blood samples before diagnostic TBLC. Two experienced radiologists assessed the extents of following HRCT patterns: ground-glass opacities (GGO), honeycombing, reticulation, traction bronchiectasis, and emphysema. Histology of TBLC were re-analyzed by two experienced pulmonary pathologists and the presence of fibroblast foci, fibrosis, giant cells, granulomas, and honeycombing were recorded., Results: In the median multivariate regression analysis, BMI (-0.19; 95% CI -0.37- -0.014; p 0.035), GGO (-0.38; 95% CI -0.61- -0.15; p 0.001), granulomas (-3.21; 95% CI -6.12- -0.30; p 0.031), and current smoking (2.49; 95% CI 0.12-4.86; p 0.040) showed independent associations with LCQ total score. BMI (1.3; 95% CI 0.20-2.42; p 0.021) and DLCO (-0.51; 95% CI -0.85 - -0.16; p 0.004) showed independent association with SGRQ total score., Conclusion: Determinants of cough-related QoL in ILD patients are multifactorial including physiological, radiological and histological parameters., (© 2024. The Author(s).)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1219/coif). HMN reports grants from the Foundation of the Finnish Anti-Tuberculosis Association and the North Savo Regional Fund of the Finnish Cultural Foundation during the current work. She also reports a grant from Duodecim for attending a congress; lecturers’ fees from Boehringer Ingelheim Finland Ltd. and Roche Ltd.; congress/travel support from Boehringer-Ingelheim Ltd., Sanofi-Genzyme Ltd. and Chiesi Ltd., all outside the submitted work. PKE reports a consulting fee from Abbvie Ltd.; congress/travel support form Mylan Ltd. and Pfizer Ltd.; participation on an Advisory Board for Astra Zeneca Ltd., all outside the submitted work. SKS owns stocks of CRISPR Therapeutics AG, Faron Pharmaceuticals Ltd. and Merck&Company, Inc. outside the submitted work. MKP reports lecturers’ fees from Boehringer-Ingelheim Finland Ltd. and Roche Ltd.; congress/travel support from Boehringer-Ingelheim Ltd. and Orion Pharma Ltd.; participation on an Advisory Board of Boehringer-Ingelheim Ltd.; personal grants from the Foundation of the Finnish Anti-Tuberculosis Association, the Jalmari and Rauha Ahokas foundation and the Kuopio region respiratory Foundation, all outside the submitted work. RLK reports lecturers’ fees from Boehringer-Ingelheim Ltd. and Roche Ltd.; congress/travel support from Roche Ltd. and Novartis Ltd.; participation on an Advisory Board of Boehringer-Ingelheim Ltd. and MSD Ltd.; being the President of the Finnish Respiratory Society between march 2017 and march 2020; grants for the study group from the Foundation of the Finnish Anti-Tuberculosis Association, the Research Foundation of the Pulmonary Diseases, the Research Foundation of North Finland, the Jalmari and Rauha Ahokas Foundation, and a state subsidy of the Oulu University Hospital, all outside the submitted work. HOK reports lecturers’ fee from Boehringer Ingelheim Finland Ltd.; congress/travel support from Astra Zeneca Ltd.; owning shares of Orion Pharma Ltd., all outside the submitted work. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

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., (© 2022. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence of honeycombing in high-resolution computed tomography (HRCT) is a recognized risk factor for shortened survival in patients with idiopathic pulmonary fibrosis (IPF), but few studies have evaluated the feasibility of exploiting other specific patterns for predicting survival. The aim of this study was to examine the extent of specific HRCT patterns in IPF and determine whether they correlate with clinical features, pulmonary function tests (PFT), and survival., Methods: Both the presence and extent of specific HRCT patterns, such as traction bronchiectasis, honeycombing, architectural distortion, reticulation, emphysema, and ground glass opacity, in 129 HRCT examinations were scored semi-quantitatively in three zones of each lung. HRCT examinations were also re-classified according to the 2011 and 2018 international statements. Correlations were calculated between the scores of specific HRCT patterns, clinical features, PFT, and patient survival., Results: The extent of traction bronchiectasis was found to be an independent risk factor of shortened survival (HR 1.227, P=0.001). Patients with a possible usual interstitial pneumonia (UIP) pattern had a better median survival than the patients with a definite UIP pattern (61 vs. 37 months, P=0.026). The extents of traction bronchiectasis, honeycombing, and architectural distortion displayed an inverse correlation with all PFT values at the time of diagnosis. There were few differences between the radiological classifications of the 2011 and 2018 international statements., Conclusions: We conclude that several specific HRCT patterns displayed a correlation with shortened survival in IPF; these may help in evaluating the risk of death in IPF patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1957). MM has received a consulting and lecture fees from Boehringer Ingelheim Finland Ltd. and congress travel costs from Roche and Boehringer Ingelheim Finland Ltd, outside the submitted work. HPK has received a lecture fee from Roche, outside the submitted work. SS owns stocks of Merck & Co, Faron Paharmaceuticals, 3M Co, and CRISPR Therapeutics, outside the submitted work. MK has received an advisory board fee from GlaxoSmithKline, outside the submitted work. MP has received lecture and consulting fees from Boehringer-Ingelheim Finland Ltd. and a congress travel cost from Roche, outside the submitted work. RK has received a congress travel cost from Orion Pharma, lecture fees from Roche and Boehringer-Ingelheim Finland Ltd., and an advisory board fee from Boehringer Ingelheim Finland Ltd, outside the submitted work. TS declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (2021 Journal of Thoracic Disease. All rights reserved.)

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.

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.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

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.

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.

Background: We studied whether ischemia-specific computed tomography (CT) findings are consistently detectable in patients who develop acute on chronic mesenteric ischemia (AOCMI), whereas absent in chronic mesenteric ischemia (CMI)., Methods: Consecutive patients with symptomatic angiography-verified atherosclerotic obstruction of the superior mesenteric artery (SMA) were categorized as AOCMI (n = 27) or CMI (n = 20). Three experienced radiologists blindly evaluated the contrast-enhanced CTs for vascular and intestinal findings. Kappa statistics was used to test interobserver agreement., Results: Two observers had substantial agreement (k = 0.66) that two thirds of AOCMI patients showed ischemia-specific CT findings (decreased bowel wall enhancement, pneumatosis, or thrombotic SMA clot); the third observer agreed only fairly regarding pneumatosis and thrombosis (k = 0.3-0.4). All observers had substantial agreement (k = 0.65-0.71) that most patients with AOCMI had unspecific intestinal findings such as mesenteric fat stranding in up to 96%, bowel lumen dilatation in 93%, and bowel wall thickening in 70%, while only few patients with CMI had such findings (due to chronic ischemic colitis) (P < 0.001)., Conclusion: One third of AOCMI patients presented without any ischemia-specific CT signs. However, any intestinal abnormality in CT together with SMA obstruction should raise suspicion of intestinal ischemia. Furthermore, clinicians need to be aware of the interobserver variability in the CT interpretation.

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.