Antioxidants (Basel). 2022 Mar 8;11(3):523. doi: 10.3390/antiox11030523.

ABSTRACT

Bleomycin (BLM) administration is associated with multifunctional proteins inflammations and induction of idiopathic pulmonary fibrosis (IPF). Lemna minor L. extract, a free-floating monocot macrophyte possesses antioxidant and anti-inflammatory potential. The aim of the study was to examine the protective effect of L. minor extract on lung protein oxidation and oxidative stress modulation by BLM-induced pulmonary fibrosis in Balb/c mice. For this purpose, the protein carbonyl content, advanced glycation end product, nitroxide protein oxidation (5-MSL), and lipid peroxidation (as MDA and ROS), in lung cells were examined. The histological examinations, collagen deposition, and quantitative measurements of IL-1β, IL-6, and TNF in lung tissues and blood were investigated. Intraperitoneal, BLM administration (0.069 U/mL; 0.29 U/kg b.w.) for 33 days, caused IPF induction in Balb/c mice. Pulmonary combining therapy was administered with L. minor at dose 120 mg/mL (0.187 mg/kg b.w.). L. minor histologically ameliorated BLM induced IPF in lung tissues. L. minor significantly modulated (p < 0.05) BLM-alterations induced in lung hydroxyproline, carbonylated proteins, 5-MSL-protein oxidation. Oxidative stress decreased levels in antioxidant enzymatic and non-enzymatic systems in the lung were significantly regulated (p < 0.05) by L. minor. L. minor decreased the IL-1β, IL-6, and TNF-α expression in lung tissues and plasma. The L. minor improves the preventive effect/defense response in specific pulmonary protein oxidation, lipid peroxidation, ROS identifications, and cytokine modulation by BLM-induced chronic inflammations, and could be a good antioxidant, anti-inflammatory, and anti-fibrotic alternative or IPF prevention involved in their pathogenesis.

PMID:35326173 | DOI:10.3390/antiox11030523

Antioxidants (Basel). 2022 Feb 28;11(3):492. doi: 10.3390/antiox11030492.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), a severe and deadly form of lung fibrosis, is widely regarded as a disease of aging. We previously demonstrated that aged mice with persistent lung fibrosis and IPF lung myofibroblasts exhibit deficient Nrf2-mediated antioxidant responses. Tecfidera is an orally administered FDA-approved drug for the treatment of multiple sclerosis, where the active pharmaceutical ingredient is dimethyl fumarate (DMF), an active Nrf2 activator. However, no studies have evaluated the efficacy of DMF for age-associated persistent lung fibrosis. Here, we demonstrate that in IPF lung fibroblasts, DMF treatment inhibited both TGF-β-mediated pro-fibrotic phenotypes and led to a reversal of established pro-fibrotic phenotypes. We also evaluated the pre-clinical efficacy of lung-targeted (inhaled) vs. systemic (oral) delivery of DMF in an aging murine model of bleomycin-induced persistent lung fibrosis. DMF or vehicle was administered daily to aged mice by oral gavage or intranasal delivery from 3-6 weeks post-injury when mice exhibited non-resolving lung fibrosis. In contrast to systemic (oral) delivery, only lung-targeted (inhaled) delivery of DMF restored lung Nrf2 expression levels, reduced lung oxidative stress, and promoted the resolution of age-dependent established fibrosis. This is the first study to demonstrate the efficacy of lung-targeted DMF delivery to promote the resolution of age-dependent established lung fibrosis.

PMID:35326142 | DOI:10.3390/antiox11030492

Nat Commun. 2022 Mar 23;13(1):1558. doi: 10.1038/s41467-022-29064-3.

ABSTRACT

Idiopathic pulmonary fibrosis is an incurable disease of unknown etiology. Acute exacerbation of idiopathic pulmonary fibrosis is associated with high mortality. Excessive apoptosis of lung epithelial cells occurs in pulmonary fibrosis acute exacerbation. We recently identified corisin, a proapoptotic peptide that triggers acute exacerbation of pulmonary fibrosis. Here, we provide insights into the mechanism underlying the processing and release of corisin. Furthermore, we demonstrate that an anticorisin monoclonal antibody ameliorates lung fibrosis by significantly inhibiting acute exacerbation in the human transforming growth factorβ1 model and acute lung injury in the bleomycin model. By investigating the impact of the anticorisin monoclonal antibody in a general model of acute lung injury, we further unravel the potential of corisin to impact such diseases. These results underscore the role of corisin in the pathogenesis of acute exacerbation of pulmonary fibrosis and acute lung injury and provide a novel approach to treating this incurable disease.

PMID:35322016 | DOI:10.1038/s41467-022-29064-3

J Med Econ. 2022 Mar 24:1-35. doi: 10.1080/13696998.2022.2054203. Online ahead of print.

ABSTRACT

AIMS: While nintedanib treatment has been shown to slow the progression of idiopathic pulmonary fibrosis (IPF) in patients across varying levels of lung function, the effect of treatment timing on outcomes has not been examined. We assessed hospitalization risk and medical costs among patients with IPF based on the timing of nintedanib initiation after IPF diagnosis.

MATERIALS AND METHODS: This retrospective administrative claims study included data from 04/01/2014-09/30/2019 for patients aged ≥40 years who initiated nintedanib within 1 year of IPF diagnosis. Patients were assigned to study cohorts based on the time from IPF diagnosis to nintedanib initiation. All-cause hospitalization and all-cause medical costs were modeled using marginal structural models including inverse probability weights to adjust for both baseline and time-varying characteristics.

RESULTS: Of 11,195 patients diagnosed with IPF during the identification period, 449 met the study selection criteria (mean age 72.3 years, 68% male, mean follow-up time 13.3 months). Adjusted hospitalization risk and medical costs both varied significantly by timing of nintedanib initiation (p < 0.001 and p = 0.020, respectively). Adjusted weighted hospitalization risk was higher among untreated vs treated patients in months 2-3, months 4-6, and months 7-12 after diagnosis (hazard ratio [95% CI] 1.97 [1.09-3.56], p = 0.026; 2.62 [1.22-5.63], p = 0.014; and 5.57 [2.31-13.45], p < 0.001, respectively). Medical costs were 69% higher for patients initiating treatment in months 2-3 vs month 1 (cost ratio [95% CI] 1.69 [1.20-2.38], p = 0.003).

LIMITATIONS: Disease severity could not be assessed because clinical data were unavailable; however, proxies such as oxygen use were included to adjust for between-cohort differences in disease severity.

CONCLUSIONS: Patients who initiate nintedanib promptly after IPF diagnosis may have reduced hospitalization risk and medical costs compared with those who start treatment later. Additional studies are warranted to improve understanding of the impact of prompt antifibrotic therapy on patient outcomes.

PMID:35321616 | DOI:10.1080/13696998.2022.2054203

Rev Med Chil. 2021 Oct;149(10):1512-1515. doi: 10.4067/s0034-98872021001001512.

ABSTRACT

We report a 68-year-old woman with a history of idiopathic pulmonary fibrosis, who had immediate skin reactions associated with the use of pirfenidone in two opportunities. In the evaluation by immunology, an allergy to pirfenidone was diagnosed. Given the urgent need for the drug, a desensitization procedure was started. The dose of the medication was increased progressively, previous premedication with cetirizine, ranitidine and montelukast. After this procedure the patient was able to tolerate the treatment with pirfenidone without cutaneous reactions.

PMID:35319642 | DOI:10.4067/s0034-98872021001001512

Andes Pediatr. 2021 Oct;92(5):667-676. doi: 10.32641/andespediatr.v92i5.3708.

ABSTRACT

Left ventricular non-compaction (LVNC) and restrictive cardiomyopathies (RCM) are rare diseases with high morbidity and mortality in the pediatric age group, particularly the restrictive. They can be diagnosed at any age even in fetal life, in isolation or association with other cardiomyopathies or congenital heart disease. The causes may be genetic, neuromuscular, metabolic, storage, or idiopathic disorders. The main morphological characteristic of LVNC is the presence of a non-compact myocar dium with numerous prominent trabeculations and deep recesses, which may results in myocardial dysfunction, malignant arrhythmias and thromboembolism. On the other hand, in RCM there is an abnormal myocardial stiffness, which generates a restrictive ventricular filling and atrial dilatation secondary. Clinically it manifested by severe diastolic dysfunction, pulmonary hypertension, arrhyth mias and sudden death. For both cardiomyopathies, the Doppler color echocardiography, electro cardiography and Holter monitoring of arrhythmias are the gold standard for diagnosis and follow up. Cardiac resonance adds information on functional assessment and quantification of myocardial fibrosis. The therapy is oriented to improve symptoms and quality of life. Patients with severe forms of LVNC and RCM may require extracorporeal ventricular support and cardiac transplantation, even in early stages of the disease. The pediatrician plays an important role in the early recognition of these pathologies for timing to referral as well as in the follow-up and screening for complications. The objective of this review is to update the clinical, genetic, diagnostic, therapeutic issues and prognostic of the LVNC and RCM.

PMID:35319572 | DOI:10.32641/andespediatr.v92i5.3708

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