Sci Rep. 2022 Mar 22;12(1):4916. doi: 10.1038/s41598-022-08965-9.

ABSTRACT

Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6-along with baseline P/F ratio and CRP levels-was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD.

PMID:35318424 | DOI:10.1038/s41598-022-08965-9

Int J Pharm. 2022 Mar 19:121685. doi: 10.1016/j.ijpharm.2022.121685. Online ahead of print.

ABSTRACT

The inclusion and nanocluster formed in cyclodextrin-metal organic framework (CD-MOF) make it a remarkable vehicle in improving the solubility and bioavailability of insoluble drugs, but rarely in elongation of drug release kinetics. In this research, an insoluble compound, 18β-glycyrrhetinic acid (GA), encapsulated in CD-MOF (GA@nano-CD-MOF) had prominent effects in the treatment of bleomycin-induced idiopathic pulmonary fibrosis in rats with an enhanced bioavailability by 6.8 times. The solubility of GA@nano-CD-MOF was 7780 times higher than that of GA, which was explained by the solubility parameter of amorphous cells constructed in silico simulation. CD-MOF imparted GA unique biphasic release kinetics, namely, GA released instantly to 52% and slowly released to 100% for a period of 5 days, which made the drug loaded particles much more flexible in pharmaceutical applications. The distribution of GA molecules in CD-MOF and drug loading priority obtained by molecular docking illustrated the formation of biphasic release mode at the molecular level combined with other characterizations of SEM, PXRD, TGA and DSC. In conclusion, CD-MOF has a unique effect to simultaneously solubilize an insoluble drug and extend its release for days as payload in highly soluble particles of γ-cyclodextrin metal-organic frameworks, which broaden the applications of drugs in specific treatment and then enhance the therapeutic effects.

PMID:35318073 | DOI:10.1016/j.ijpharm.2022.121685

BMC Vet Res. 2022 Mar 22;18(1):111. doi: 10.1186/s12917-022-03191-x.

ABSTRACT

BACKGROUND: Interstitial lung disease is a heterogeneous group of conditions characterized by severe radiographic changes and clinicopathological findings. However, in the vast majority of cases, the cause remains unknown.

CASE DESCRIPTION: In the present study, we reported the clinical case of a 3 years old female Bull Terrier presented in October 2020 to the Advanced Diagnostic Imaging Department of the Turin Veterinary Teaching Hospital with a progressive pulmonary illness characterized by dyspnea, exercise intolerance, and a diffuse and severe pulmonary interstitial pattern at imaging investigations. Considering the clinical findings, the dog was included in a serological survey for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in companion animals, showing positive results. Due to the further clinical worsening, the owners opted for euthanasia. At necroscopy, dog showed severe and chronic bronchopneumonia compatible with a Canine Idiopathic Pulmonary Fibrosis and with serological features linked to a SARS-CoV-2 infection.

CONCLUSIONS: The comparison of these lesions with those reported in humans affected by Coronavirus Disease 2019 (COVID-19) supports the hypothesis that these findings may be attributable to the post-acute sequelae of SARS-CoV-2 infection in a dog with breed predisposition to Canine Idiopathic Pulmonary Fibrosis (CIPF), although direct evidence of SARS-CoV-2 by molecular or antigenic approaches remained unsolved.

PMID:35317791 | DOI:10.1186/s12917-022-03191-x

Nanomedicine (Lond). 2022 Mar 22. doi: 10.2217/nnm-2021-0447. Online ahead of print.

ABSTRACT

The physiochemical properties of drugs used in treating inflammation-associated lung diseases (i.e., asthma, chronic obstructive pulmonary disease, pulmonary fibrosis) play an important role in determining the effectiveness of formulations. Most commonly used drugs are associated with low solubility, low stability and rapid clearance, thus resulting in low bioavailability and therapeutic index. This review focuses on current trends and development of drugs (i.e., corticosteroids, long-acting β-agonists and biomacromolecules such as DNA, siRNA and mRNA) employed to treat inflammatory lung diseases. In addition, this review includes the current challenges of and future perspective with regard to nanotechnology in the treatment of inflammatory lung diseases.

PMID:35315290 | DOI:10.2217/nnm-2021-0447

Radiat Oncol. 2022 Mar 21;17(1):56. doi: 10.1186/s13014-022-02027-0.

ABSTRACT

BACKGROUND: Interstitial pneumonia (IP) is a disease with a poor prognosis. In addition, IP patients are more likely to develop lung cancer. Since IP patients frequently develop toxicities during cancer treatment, minimally invasive cancer treatment is warranted for such patients to maintain their quality of life. This study retrospectively investigated the efficacy and safety of proton therapy (PT) for non-small cell lung cancer (NSCLC) in patients with IP.

METHODS: Twenty-nine NSCLC patients with IP were treated with PT between September 2013 and December 2019. The patients had stage IA to IIIB primary NSCLC. Ten of the 29 patients exhibited the usual interstitial pneumonia pattern. The prescribed dose was 66-74 Grays (relative biological effectiveness) in 10-37 fractions.

RESULTS: The median follow-up period was 21.1 months [interquartile range (IQR), 15.6-37.3] for all patients and 37.2 months (IQR, 24.0-49.9) for living patients. The median patient age was 77 years (IQR, 71-81). The median planning target volume was 112.0 ml (IQR, 56.1-246.3). The 2-year local control, progression-free survival, and overall survival rates were 85% (95% confidence interval: 57-95), 30% (15-47), and 45% (26-62), respectively. According to the Common Terminology Criteria for Adverse Events (version 4.0), grade 3 acute radiation pneumonitis (RP) was observed in 1 patient. Two patients developed grade 3 late RP, but no other patients experienced serious toxicities. The patients' quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 and SF-36) scores had not changed after 3 months.

CONCLUSIONS: PT may be a relatively safe treatment for NSCLC patients with IP, without deteriorating quality of life scores within 3 months.

PMID:35313905 | DOI:10.1186/s13014-022-02027-0

Arch Bronconeumol. 2021 Jun 17:S0300-2896(21)00183-6. doi: 10.1016/j.arbres.2021.05.025. Online ahead of print.

NO ABSTRACT

PMID:35312599 | DOI:10.1016/j.arbres.2021.05.025

Arch Bronconeumol. 2022 Feb 24:S0300-2896(22)00081-3. doi: 10.1016/j.arbres.2022.01.010. Online ahead of print.

ABSTRACT

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

PMID:35312523 | DOI:10.1016/j.arbres.2022.01.010

Arch Bronconeumol. 2022 Jan 17:S0300-2896(22)00015-1. doi: 10.1016/j.arbres.2022.01.003. Online ahead of print.

ABSTRACT

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

PMID:35312522 | DOI:10.1016/j.arbres.2022.01.003

Arch Bronconeumol. 2022 Jan 5:S0300-2896(22)00002-3. doi: 10.1016/j.arbres.2021.12.006. Online ahead of print.

ABSTRACT

In addition to idiopathic pulmonary fibrosis (IPF), other diffuse interstitial lung diseases (ILD) are also associated with pulmonary fibrosis and occur in a variable proportion of patients, depending on the entity. The name given to this fibrotic component, that may progress despite treatment, is progressive pulmonary fibrosis (PPF). In this context, PPF is not an entity per se but a common clinical condition or behavior that may occur in association with different types of fibrosing diffuse ILDs, compromising patient prognosis. PPF is identified from worsening clinical, physiological, and/or radiological criteria during patient follow-up. Randomized clinical trials in patients with IPF or progressive non-IPF ILD have shown that treatment with antifibrotic drugs, either nintedanib or pirfenidone, slows progression. We are seeing the start of a new era in the clinical management of this subgroup of patients, offering the perfect opportunity for exploring still uncharted territories.

PMID:35312511 | DOI:10.1016/j.arbres.2021.12.006

Front Immunol. 2022 Mar 3;13:730186. doi: 10.3389/fimmu.2022.730186. eCollection 2022.

ABSTRACT

Currently, the aetiology and pathogenesis of idiopathic pulmonary fibrosis (IPF) are still largely unclear. Moreover, patients with IPF exhibit a considerable difference in clinical presentation, treatment, and prognosis. Optimal biomarkers or models for IPF prognosis are lacking. Therefore, this study quantified the levels of various hallmarks using a single-sample gene set enrichment analysis algorithm. The hazard ration was calculated using Univariate Cox regression analysis based on the transcriptomic profile of bronchoalveolar lavage cells and clinical survival information. Afterwards, weighted Gene Co-expression Network Analysis was performed to construct a network between gene expression, inflammation response, and hypoxia. Subsequently, univariate Cox, random forest, and multivariate Cox regressions were applied to develop a robust inflammation and hypoxia-related gene signature for predicting clinical outcomes in patients with IPF. Furthermore, a nomogram was constructed to calculate risk assessment. The inflammation response and hypoxia were identified as latent risk factors for patients with IPF. Five genes, including HS3ST1, WFDC2, SPP1, TFPI, and CDC42EP2, were identified that formed the inflammation-hypoxia-related gene signature. Kaplan-Meier plotter showed that the patients with high-risk scores had a worse prognosis than those with low-risk scores in training and validation cohorts. The time-dependent concordance index and the receiver operating characteristic analysis revealed that the risk model could accurately predict the clinical outcome of patients with IPF. Therefore, this study contributes to elucidating the role of inflammation and hypoxia in IPF, which can aid in assessing individual prognosis and personalised treatment decisions.

PMID:35309336 | PMC:PMC8929415 | DOI:10.3389/fimmu.2022.730186

Cureus. 2022 Mar 11;14(3):e23063. doi: 10.7759/cureus.23063. eCollection 2022 Mar.

ABSTRACT

OBJECTIVE: Interstitial lung disease (ILD) can be complicated by comorbidities, particularly pulmonary embolism (PE). We aimed to assess the prevalence of PE in ILD patients.

METHODS: Our study is a cross-sectional retrospective study conducted on ILD cases diagnosed between January 1, 2010, and June 30, 2021. Out of the total ILD cases (n = 153), we enrolled for analysis only those who underwent a computed tomography pulmonary angiography (CTPA) (n = 48). We recorded the number of patients who had a PE event on CTPA, gender, age at PE and ILD diagnoses, a chronology of PE with ILD diagnosis, PE characteristics, PE therapy, type of ILD, radiographic progression of ILD, presence of pulmonary hypertension, and mortality.

RESULTS: Seven patients out of 48, had PE (14.6%). The mean age at the time of PE diagnosis was 70 ± 9.73 years. No statistical difference existed between the PE and non-PE groups regarding gender predominance or the age at ILD diagnosis. All of the identified PE events (n = 7) were segmental (100%), one was saddle PE (14.3%) and one was recurrent (14.3%). No PE events were diagnosed prior to ILD diagnosis, three patients (42.9%) had a simultaneous diagnosis of PE and ILD, and four patients (57.1%) were diagnosed with a PE after ILD diagnosis by a mean time of eight months. No difference in ILD radiographic progression, pulmonary hypertension, or mortality between the two groups was found.

CONCLUSION: PE is not uncommon in ILD and needs to be ruled out, especially in patients with worsening respiratory status.

PMID:35308192 | PMC:PMC8920788 | DOI:10.7759/cureus.23063

Respir Investig. 2022 Mar 17:S2212-5345(22)00018-1. doi: 10.1016/j.resinv.2022.02.002. Online ahead of print.

ABSTRACT

We describe a rare case of a 20-year-old Japanese man with idiopathic pulmonary hemosiderosis (IPH) recurrence in adults with childhood onset (racIPH). IPH commonly occurs in children, and data regarding racIPH are lacking. A review of the literature showed that only five cases of racIPH have been reported (including the present case) and that racIPH shows features that are intermediate between childhood- and adult-onset IPH with respect to age and a lower frequency of smoking history. We also found that the degree of anemia was usually not severe, and a favorable response to corticosteroid therapy is expected in racIPH.

PMID:35307363 | DOI:10.1016/j.resinv.2022.02.002

J Comp Pathol. 2022 Apr;192:23-32. doi: 10.1016/j.jcpa.2022.01.005. Epub 2022 Feb 23.

ABSTRACT

Acute interstitial pneumonia (AIP) is a significant disease of cattle and many aetiologies have been implicated on the basis of the characteristic pathological lesions. Bovine respiratory syncytial virus (BRSV) is one of the key aetiological factors in bovine respiratory disease complex and several studies have suggested, controversially, that BRSV may be an underlying cause of bovine AIP. BRSV infection is known to cause several distinctive histopathological changes, including epithelial syncytia formation and intracytoplasmic viral inclusions. However, distinguishing bovine AIP from BRSV-related pneumonia by clinical presentation, gross pathology or histopathology can sometimes be challenging. In order to identify the potential distinguishing features, we compared the histopathological findings of AIP that were, and were not, associated with BRSV infection in naturally occurring cases. We found that multinucleated giant cells were more frequently identified in cattle with AIP while bronchiolitis was more common in BRSV-infected cattle. However, this was not considered a sole indicator of either disease group. Statistically, we identified that a combination of several histopathological features, including alveolar septal necrosis, presence of multinucleated giant cells and bronchiolitis, can serve as an excellent indicator for distinguishing between idiopathic AIP and BRSV-related pneumonia, with a strong statistical significance (P = 0.0004). Based on the results of this retrospective study, we present a histopathological scoring system for predicting BRSV-associated AIP.

PMID:35305711 | DOI:10.1016/j.jcpa.2022.01.005

Respir Res. 2022 Mar 19;23(1):62. doi: 10.1186/s12931-022-01976-0.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive form of fibrosing interstitial pneumonia with poor survival. This study provides insight into the epidemiology, cost, and disease course of IPF in Germany.

METHODS: A cohort of incident patients with IPF (n = 1737) was identified from German claims data (2014-2019). Incidence and prevalence rates were calculated and adjusted for age differences compared with the overall German population. All-cause and IPF-related healthcare resource utilization as well as associated costs were evaluated per observed person-year (PY) following the initial IPF diagnosis. Finally, Kaplan-Meier analyses were performed to assess time from initial diagnosis to disease deterioration (using three proxy measures: non-elective hospitalization, IPF-related hospitalization, long-term oxygen therapy [LTOT]); antifibrotic therapy initiation; and all-cause death.

RESULTS: The cumulative incidence of IPF was estimated at 10.7 per 100,000 individuals in 2016, 10.9 in 2017, 10.5 in 2018, and 9.6 in 2019. The point prevalence rates per 100,000 individuals for the respective years were 21.7, 23.5, 24.1, and 24.1. On average, ≥ 14 physician visits and nearly two hospitalizations per PY were observed after the initial IPF diagnosis. Of total all-cause direct costs (€15,721/PY), 55.7% (€8754/PY) were due to hospitalizations and 29.1% (€4572/PY) were due to medication. Medication accounted for 49.4% (€1470/PY) and hospitalizations for 34.8% (€1034/PY) of total IPF-related direct costs (€2973/PY). Within 2 years of the initial IPF diagnosis (23.6 months), 25% of patients died. Within 5 years of diagnosis, 53.1% of patients had initiated LTOT; only 11.6% were treated with antifibrotic agents. The median time from the initial diagnosis to the first non-elective hospitalization was 5.5 months.

CONCLUSION: The incidence and prevalence of IPF in Germany are at the higher end of the range reported in the literature. The main driver for all-cause cost was hospitalization. IPF-related costs were mainly driven by medication, with antifibrotic agents accounting for around one-third of the total medication costs even if not frequently prescribed. Most patients with IPF do not receive pharmacological treatment, highlighting the existing unmet medical need for effective and well-tolerated therapies.

PMID:35305632 | DOI:10.1186/s12931-022-01976-0

Rev Mal Respir. 2022 Mar 14:S0761-8425(22)00026-2. doi: 10.1016/j.rmr.2022.01.005. Online ahead of print.

ABSTRACT

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated.

METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale.

RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis.

CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

PMID:35304014 | DOI:10.1016/j.rmr.2022.01.005

Respir Res. 2022 Mar 18;23(1):61. doi: 10.1186/s12931-022-01980-4.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with limited treatment options. A phase 2 trial (NCT01766817) showed that twice-daily treatment with BMS-986020, a lysophosphatidic acid receptor 1 (LPA1) antagonist, significantly decreased the slope of forced vital capacity (FVC) decline over 26 weeks compared with placebo in patients with IPF. This analysis aimed to better understand the impact of LPA1 antagonism on extracellular matrix (ECM)-neoepitope biomarkers and lung function through a post hoc analysis of the phase 2 study, along with an in vitro fibrogenesis model.

METHODS: Serum levels of nine ECM-neoepitope biomarkers were measured in patients with IPF. The association of biomarkers with baseline and change from baseline FVC and quantitative lung fibrosis as measured with high-resolution computed tomography, and differences between treatment arms using linear mixed models, were assessed. The Scar-in-a-Jar in vitro fibrogenesis model was used to further elucidate the antifibrotic mechanism of BMS-986020.

RESULTS: In 140 patients with IPF, baseline ECM-neoepitope biomarker levels did not predict FVC progression but was significantly correlated with baseline FVC and lung fibrosis measurements. Most serum ECM-neoepitope biomarker levels were significantly reduced following BMS-986020 treatment compared with placebo, and several of the reductions correlated with FVC and/or lung fibrosis improvement. In the Scar-in-a-Jar in vitro model, BMS-986020 potently inhibited LPA1-induced fibrogenesis.

CONCLUSIONS: BMS-986020 reduced serum ECM-neoepitope biomarkers, which were previously associated with IPF prognosis. In vitro, LPA promoted fibrogenesis, which was LPA1 dependent and inhibited by BMS-986020. Together these data elucidate a novel antifibrotic mechanism of action for pharmacological LPA1 blockade. Trial registration ClinicalTrials.gov identifier: NCT01766817; First posted: January 11, 2013; https://clinicaltrials.gov/ct2/show/NCT01766817 .

PMID:35303880 | DOI:10.1186/s12931-022-01980-4

Rheumatology (Oxford). 2022 Mar 18:keac184. doi: 10.1093/rheumatology/keac184. Online ahead of print.

ABSTRACT

OBJECTIVE: The prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is difficult to predict because of the variable clinical course. This study aimed to determine the prognostic value of an automated quantification system (AQS) in RA-ILD.

METHODS: We retrospectively analysed the clinical data and high-resolution computed tomography (HRCT) images of 144 patients with RA-ILD. Quantitative lung fibrosis (QLF, sum of reticulation and traction bronchiectasis) and ILD (QILD; sum of QLF, honeycombing [QHC], and ground-glass opacity [QGG]) scores were measured using the AQS.

RESULTS: The mean age was 61.2 years, 43.8% of the patients were male, and the 5-year mortality rate was 30.5% (median follow-up, 52.2 months). Non-survivors showed older age, higher erythrocyte sedimentation rate (ESR), and greater AQS scores than survivors. In multivariable Cox analysis, higher QLF, QHC, and QILD scores were independent prognostic factors along with older age and higher ESR. In receiver-operating characteristic curve analysis, the QLF score showed better performance in predicting 5-year mortality than the QHC and QGG scores but was similar to the QILD score. Patients with high QLF scores (≥12% of total lung volume) showed higher 5-year mortality (50% vs. 17.4%, P<0.001) than those with low QLF scores and similar survival outcome to patients with idiopathic pulmonary fibrosis (IPF). Combining with clinical variables (age, ESR) further improved the performance of QLF score in predicting 5-year mortality.

CONCLUSION: QLF scores might be useful for predicting prognosis in patients with RA-ILD. High QLF scores differentiate a poor prognostic phenotype similar to IPF.

PMID:35302602 | DOI:10.1093/rheumatology/keac184

Eur J Ophthalmol. 2022 Mar 18:11206721221088259. doi: 10.1177/11206721221088259. Online ahead of print.

ABSTRACT

OBJECTIVES: Dry eye disease (DED) is arguably the most frequent ocular disease encountered in ophthalmic clinical practice. DED is frequently an underestimated condition causing a significant impact on visual function and quality of life. Many systemic autoimmune diseases (SAIDs) are related to moderate to severe DED. The main objective of this review is to enhance the awareness among ophthalmologists of the potential association of an underlying SAID in a high-risk patient with DED.

METHODS: An exhaustive literature search was performed in the National Library of Medicine's Pubmed, Scopus, Web of Science, and Google Scholar databases for all English language articles published until November 2021. The main keywords included "dry eye disease" associated with autoimmune, connective tissue, endocrine, gastrointestinal, hematopoietic, vascular, and pulmonary diseases. Case reports, series, letters to the editor, reviews, and original articles were included.

RESULTS: Although DED is frequently associated with SAIDs, its diagnosis is commonly delayed or missed, producing significant complications, including corneal ulceration, melting, scleritis, uveitis, and optic neuritis resulting in severe complications detrimental to visual function and quality of life. SAID should be suspected in a woman, 30 to 60 years old with a family history of autoimmunity, presenting with DED symptoms and extraocular manifestations including arthralgias, dry mouth, unexplained weight and hair loss, chronic fatigue, heat or cold intolerance, insomnia, and mood disorders.

CONCLUSIONS: Establishing the correct diagnosis and treatment of DED associated with SAIDs is crucial to avoid its significant burden and severe ocular complications.

PMID:35300528 | DOI:10.1177/11206721221088259

ERJ Open Res. 2022 Mar 14;8(1):00541-2021. doi: 10.1183/23120541.00541-2021. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Physical activity contributes to improving respiratory symptoms. However, validated end-points are few, and there is limited consensus about what is a clinically meaningful improvement for patients. This review summarises the evidence to date on the range of physical activity end-points used in COPD, asthma and idiopathic pulmonary fibrosis (IPF) whilst evaluating their appropriateness as end-points in trials and their relation to patients' everyday life.

METHODS: Trials reporting physical activity end-points were collected using Citeline's database Trialtrove; this was supplemented by searches in PubMed.

RESULTS: The daily-patient-reported outcome (PRO)active and clinical visit-PROactive physical activity composite end-points appeared superior at capturing the full experience of physical activity in patients with COPD and were responsive to bronchodilator intervention. Time spent in moderate-to-vigorous physical activity is a recently validated end-point for IPF that correlates with exercise capacity and quality of life. Step count appears the best available physical activity measure for asthma, which consistently declines with worse disease status. However, evidence suggests a time lag before significant improvement in step count is seen which may reflect the impact of human behaviour on physical activity.

CONCLUSIONS: Physical activity represents a challenging domain to accurately measure. This is the first review evaluating physical activity measures used specifically within the respiratory field. Whilst physical activity can be effectively captured using PROactive in patients with COPD, this review highlights the unmet need for novel patient-focused end-points in asthma and IPF which would offer opportunities to develop efficacious medicines with impact on patients' therapeutic care and quality of life.

PMID:35295234 | PMC:PMC8918933 | DOI:10.1183/23120541.00541-2021

ERJ Open Res. 2022 Mar 14;8(1):00591-2021. doi: 10.1183/23120541.00591-2021. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: There are substantial advances in diagnosis and treatment for idiopathic pulmonary fibrosis (IPF), but without much evidence available on recent mortality and survival trends.

METHODS: A narrative synthesis approach was used to investigate the mortality trends, then meta-analyses for survival trends were carried out based on various time periods.

RESULTS: Six studies reported the mortality data for IPF in 22 countries, and 62 studies (covering 63 307 patients from 20 countries) reported survival data for IPF. Age-standardised mortality for IPF varied from ∼0.5 to ∼12 per 100 000 population per year after year 2000. There were increased mortality trends for IPF in Australia, Brazil, Belgium, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Lithuania, the Netherlands, Poland, Portugal, Spain, Sweden and UK, while Austria, Croatia, Denmark, Romania and the USA showed decreased mortality trends. The overall 3-year and 5-year cumulative survival rates (CSRs) were 61.8% (95% CI 58.7-64.9; I2=97.1%) and 45.6% (95% CI 41.5-49.7; I2=97.7%), respectively. Prior to 2010, the pooled 3-year CSR was 59.9% (95% CI 55.8-64.1; I2=95.8%), then not significantly (p=0.067) increased to 66.2% (95% CI 62.9-69.5; I2=92.6%) in the 2010s decade. After excluding three studies in which no patients received antifibrotics after year 2010, the pooled 3-year CSRs significantly (p=0.039) increased to 67.4% (95% CI 63.9-70.9; I2=93.1%) in the 2010s decade.

DISCUSSION: IPF is a diagnosis associated with high mortality. There was no observed increasing survival trend for patients with IPF before year 2010, with then a switch to an improvement, which is probably multifactorial.

PMID:35295232 | PMC:PMC8918939 | DOI:10.1183/23120541.00591-2021