Toxicol Appl Pharmacol. 2022 Jan 25:115885. doi: 10.1016/j.taap.2022.115885. Online ahead of print.

ABSTRACT

In a Phase 2 clinical trial, BMS-986020, a lysophosphatidic acid receptor-1 (LPA1) antagonist, produced hepatobiliary toxicity (increased ALT, AST, and ALP; cholecystitis) and increases in plasma bile acids (BA). Nonclinical investigations conducted to identify a potential mechanism(s) for this toxicity examined BMS-986020 and two LPA1 antagonists structurally distinct from BMS-986020 (BMS-986234 and BMS-986278). BMS-986020 inhibited hepatic BA efflux transporters BSEP (IC50 1.8 μM), MRP3 (IC50 22 μM), and MRP4 (IC50 6.2 μM) and inhibited BA canalicular efflux in human hepatocytes (68% at 10 μM). BMS-986020 inhibited mitochondrial function (basal and maximal respiration, ATP production, and spare capacity) in human hepatocytes and cholangiocytes at ≥10 μM and inhibited phospholipid efflux in human hepatocytes (MDR3 IC50 7.5 μM). A quantitative systems toxicology analysis (DILIsym®), considering pharmacokinetics, BA homeostasis, mitochondrial function, oxidative phosphorylation, and reactive intermediates performed for BMS-986020 recapitulated clinical findings ascribing the effects to BA transporter and mitochondrial electron transport chain inhibition. BMS-986234 and BMS-986278 minimally inhibited hepatic BA transporters (IC50 ≥20 μM) and did not inhibit MDR3 activity (IC50 >100 μM), nor did BMS-986234 inhibit BA efflux (≤50 μM) or mitochondrial function (≤30 μM) (BMS-986278 not evaluated). Multiple mechanisms may be involved in the clinical toxicity observed with BMS-986020. The data indicate that this toxicity was unrelated to LPA1 antagonism since the mechanisms that likely influenced the adverse clinical outcome of BMS-986020 were not observed with equipotent LPA1 antagonists BMS-986234 and BMS-986278. This conclusion is consistent with the lack of hepatobiliary toxicity in nonclinical and clinical safety studies with BMS-986278.

PMID:35090952 | DOI:10.1016/j.taap.2022.115885

Eur Respir J. 2022 Jan 27;59(1):2102147. doi: 10.1183/13993003.02147-2021. Print 2022 Jan.

NO ABSTRACT

PMID:35086844 | DOI:10.1183/13993003.02147-2021

Eur Respir J. 2022 Jan 27:2102711. doi: 10.1183/13993003.02711-2021. Online ahead of print.

NO ABSTRACT

PMID:35086833 | DOI:10.1183/13993003.02711-2021

Eur Respir J. 2022 Jan 27:2103124. doi: 10.1183/13993003.03124-2021. Online ahead of print.

NO ABSTRACT

PMID:35086831 | DOI:10.1183/13993003.03124-2021

Eur Respir J. 2022 Jan 27:2003697. doi: 10.1183/13993003.03697-2020. Online ahead of print.

ABSTRACT

Although DNA methylation has been recognized in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the exact mechanisms, however, are yet to be fully addressed. Herein, we demonstrated that lungs originated from IPF patients and mice after bleomycin (BLM)-induced pulmonary fibrosis are characterized by the altered DNA methylation along with overexpression of methyl-CpG-binding domain 2 (MBD2) in myofibroblasts, a reader responsible for interpreting DNA methylome-encoded information. Specifically, depletion of Mbd2 in fibroblasts or myofibroblasts protected mice from BLM-induced pulmonary fibrosis coupled with a significant reduction of fibroblast differentiation. Mechanistically, TGF-β1 induced a positive feedback regulatory loop between transforming growth factor-β receptor I (TβRI), Smad3 and Mbd2, and erythroid differentiation regulator 1 (Erdr1). TGF-β1 induced fibroblasts to undergo a global DNA hypermethylation along with Mbd2 overexpression in a TβRI/Smad3 dependent manner, and Mbd2 selectively bound to the methylated CpG DNA within the Erdr1 promoter to repress its expression, through which it enhances TGF-β/Smads signaling to promote fibroblast differentiating into myofibroblast and exacerbate pulmonary fibrosis. Therefore, enhancing Erdr1 expression strikingly reversed established pulmonary fibrosis. Collectively, our data support that strategies aimed at silencing Mbd2 or increasing Erdr1 could be viable therapeutic approaches for prevention and treatment of pulmonary fibrosis in clinical settings.

PMID:35086828 | DOI:10.1183/13993003.03697-2020

Clin Transl Med. 2022 Jan;12(1):e711. doi: 10.1002/ctm2.711.

ABSTRACT

Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients. The disrupted LDL-LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr-deficient (Ldlr-/-) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast-like endothelial and ATII cells and significantly earlier and more severe fibrotic response compared to wild-type mice. In vitro experiments revealed that apoptosis and TGF-β1 production were induced by LDL, while fibroblast-like cell accumulation and ET-1 expression were induced by LDLR knockdown. Treatment of fibroblasts with LDL or culture medium derived from LDL-pretreated endothelial or epithelial cells led to obvious fibrotic responses in vitro. Similar results were observed after LDLR knockdown operation. These results suggest that disturbed LDL-LDLR metabolism contributes in various ways to the malfunction of endothelial and epithelial cells, and fibroblasts during pulmonary fibrogenesis. In addition, pharmacological restoration of LDLR levels by using a combination of atorvastatin and alirocumab inhibited BLM-induced LDL elevation, apoptosis, fibroblast-like cell accumulation and mitigated PF in mice. Therefore, LDL-LDLR may serve as an important mediator in PF, and LDLR enhancing strategies may have beneficial effects on PF.

PMID:35083881 | DOI:10.1002/ctm2.711

Br J Pharmacol. 2022 Jan 26. doi: 10.1111/bph.15806. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with multiple contributing factors. Insulin-like growth factor 1 receptor (IGF1R), with a reciprocal function to Aryl hydrocarbon receptor (AhR), is known to be involved in the development of airway inflammation. However, the exact relationship between IGF1R and AhR in lung fibrogenesis is unclear. This study aimed to investigate the cascade pathway involving IGF1R and AhR in IPF.

EXPERIMENTAL APPROACH: The AhR and IGF1R expressions were determined in the lungs of IPF patients and in a rodent fibrosis model. Pulmonary fibrosis was evaluated in bleomycin (BLM)-induced lung injury in wild type and AhR knockout (AhR-/- ) mice. The effects of IGF1R inhibition and AhR activation in vitro on TGF-β1-induced epithelial-mesenchymal transition (EMT) in Beas2B cells and in vivo on BLM-exposed mice were also examined.

KEY RESULTS: There were increased IGF1R levels but diminished AhR expression in the lung tissues of IPF patients and BLM-induced mice. Knockout of AhR aggravated lung fibrosis, while the use of IGF1R inhibitor and AhR agonist significantly attenuated such effects and inhibited TGF-β1-induced EMT in Beas2B cells. Both TGF-β1 and BLM markedly suppressed AhR expression through endoplasmic reticulum (ER) stress and consequently, IGF1R activation. The IGF1R inhibitor and specific knockdown of IGF1R reversed the activation of the TGF-β1 signal pathway.

CONCLUSION AND IMPLICATIONS: In the development of IPF, AhR and IGF1R play opposite roles via the TGF-β/Smad/STAT signaling cascade. The AhR/IGF1R axis is a potential target for the treatment of lung injury and fibrosis.

PMID:35083738 | DOI:10.1111/bph.15806

Gen Thorac Cardiovasc Surg. 2022 Jan 27. doi: 10.1007/s11748-021-01764-5. Online ahead of print.

ABSTRACT

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is among the most fatal postoperative complications of lung resection in patients with IPF. Non-small-cell lung cancer (NSCLC) with IPF exhibits basal segment dominance. Treatment options for these lesions include lobectomy or basal segment segmentectomies. However, these procedures potentially increase risks of AE due to surgical stress including prolonged operative time and loss of pulmonary function. Therefore, as an alternative to these procedures, we developed a simple and practical deep wedge resection technique for basal segments. Our technique is minimally invasive and quick and simple approach in patients with NSCLC and IPF.

PMID:35083641 | DOI:10.1007/s11748-021-01764-5

ERJ Open Res. 2022 Jan 24;8(1):00422-2021. doi: 10.1183/23120541.00422-2021. eCollection 2022 Jan.

ABSTRACT

Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the potential to be challenging. The variable course and poor prognosis of IPF complicate discussions around life expectancy but should not prevent clinicians from having meaningful conversations about patients' fears and needs, while acknowledging uncertainties. Patients want information about the course of their disease and management options, but the provision of information needs to be individualised to the needs and preferences of the patient. Communication from clinicians should be empathetic and take account of the patient's perceptions and concerns. Models, tools and protocols are available that can help clinicians to improve their interactions with patients. In this article, we consider the difficulties inherent in discussions with patients with IPF and their loved ones, and how clinicians might communicate with patients more effectively, from breaking the news about the diagnosis to providing support throughout the course of the disease.

PMID:35083325 | PMC:PMC8784894 | DOI:10.1183/23120541.00422-2021

ERJ Open Res. 2022 Jan 24;8(1):00583-2021. doi: 10.1183/23120541.00583-2021. eCollection 2022 Jan.

ABSTRACT

AIM: The prevalence of monogenic disease-causing gene variants in lung transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.

PATIENTS AND METHODS: We retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.

RESULTS: 15 patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. 11 patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.

CONCLUSION: Genetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.

PMID:35083318 | PMC:PMC8784759 | DOI:10.1183/23120541.00583-2021

ERJ Open Res. 2022 Jan 24;8(1):00549-2021. doi: 10.1183/23120541.00549-2021. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Patients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common computed tomography (CT) parenchymal features is unknown.

METHODS: 660 IPAH and PH-CLD patients assessed between 2001 and 2019 were included. Reports for all CT scans 1 year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan-Meier analysis were performed.

RESULTS: At univariate analysis of the whole cohort, centrilobular ground-glass (CGG) changes (hazard ratio, HR 0.29) and ground-glass opacification (HR 0.53) predicted improved survival, while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (all p<0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and diffusing capacity of the lung for carbon monoxide (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46%, respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema.

INTERPRETATION: Routine clinical reports of CT lung parenchymal disease identify groups of patients with IPAH and PH-CLD with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.

PMID:35083317 | PMC:PMC8784758 | DOI:10.1183/23120541.00549-2021

ERJ Open Res. 2022 Jan 24;8(1):00597-2021. doi: 10.1183/23120541.00597-2021. eCollection 2022 Jan.

ABSTRACT

The PERSEIDS study aimed to estimate incidence/prevalence of interstitial lung diseases (ILDs), fibrosing interstitial lung diseases (F-ILDs), idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated ILD (SSc-ILD), other non-IPF F-ILDs and their progressive-fibrosing (PF) forms in six European countries, as current data are scarce. This retrospective, two-phase study used aggregate data (2014-2018). In Phase 1, incident/prevalent cases of ILDs above were identified from clinical databases through an algorithm based on codes/keywords, and incidence/prevalence was estimated. For non-IPF F-ILDs, the relative percentage of subtypes was also determined. In Phase 2, a subset of non-IPF F-ILD cases was manually reviewed to determine the percentage of PF behaviour and usual interstitial pneumonia-like (UIP-like) pattern. A weighted mean percentage of progression was calculated for each country and used to extrapolate incidence/prevalence of progressive-fibrosing ILDs (PF-ILDs). In 2018, incidence/105 person-years ranged between 9.4 and 83.6 (ILDs), 7.7 and 76.2 (F-ILDs), 0.4 and 10.3 (IPF), 6.6 and 71.7 (non-IPF F-ILDs), and 0.3 and 1.5 (SSc-ILD); and prevalence/105 persons ranged between 33.6 and 247.4 (ILDs), 26.7 and 236.8 (F-ILDs), 2.8 and 31.0 (IPF), 22.3 and 205.8 (non-IPF F-ILDs), and 1.4 and 10.1 (SSc-ILD). Among non-IPF F-ILDs, sarcoidosis was the most frequent subtype. PF behaviour and UIP-like pattern were present in a third of non-IPF F-ILD cases each and hypersensitivity pneumonitis showed the highest percentage of progressive behaviour. Incidence of PF-ILDs ranged between 2.1 and 14.5/105 person-years, and prevalence between 6.9 and 78.0/105 persons. To our knowledge, PERSEIDS is the first study assessing incidence, prevalence and rate of progression of ILDs across several European countries. Still below the threshold for orphan diseases, the estimates obtained were higher and more variable than reported in previous studies, but differences in study design/population must be considered.

PMID:35083316 | PMC:PMC8784757 | DOI:10.1183/23120541.00597-2021

Front Pharmacol. 2022 Jan 10;12:812166. doi: 10.3389/fphar.2021.812166. eCollection 2021.

ABSTRACT

Obesity is an epidemic worldwide and the obese people suffer from a range of respiratory complications including fibrotic changes in the lung. The influence of obesity on the lung is multi-factorial, which is related to both mechanical injury and various inflammatory mediators produced by excessive adipose tissues, and infiltrated immune cells. Adiposity causes increased production of inflammatory mediators, for example, cytokines, chemokines, and adipokines, both locally and in the systemic circulation, thereby rendering susceptibility to respiratory diseases, and altered responses. Lung fibrosis is closely related to chronic inflammation in the lung. Current data suggest a link between lung fibrosis and diet-induced obesity, although the mechanism remains incomplete understood. This review summarizes findings on the association of lung fibrosis with obesity, highlights the role of several critical inflammatory mediators (e.g., TNF-α, TGF-β, and MCP-1) in obesity related lung fibrosis and the implication of obesity in the outcomes of idiopathic pulmonary fibrosis patients.

PMID:35082682 | PMC:PMC8784552 | DOI:10.3389/fphar.2021.812166

Tuberc Respir Dis (Seoul). 2022 Jan 27. doi: 10.4046/trd.2021.0104. Online ahead of print.

ABSTRACT

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

PMID:35081692 | DOI:10.4046/trd.2021.0104

Clin Respir J. 2022 Jan 26. doi: 10.1111/crj.13475. Online ahead of print.

ABSTRACT

BACKGROUND: Serum Krebs von den Lungen-6 (KL-6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF).

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of KL-6 and whether the expression value of KL-6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL-6 level.

DESIGN: We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed.

RESULTS: The tests showed that there is a significant elevation of KL-6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL-6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL-6 levels. KL-6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival.

CONCLUSIONS: It is identified that serum KL-6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis.

PMID:35081277 | DOI:10.1111/crj.13475

BMC Cancer. 2022 Jan 25;22(1):110. doi: 10.1186/s12885-021-08912-3.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common type of interstitial pneumonia. Lung cancer, mainly non-small cell lung cancer (NSCLC), is a complication of idiopathic pulmonary fibrosis. IPF is also an independent risk factor of lung cancer. Some studies have shown that the complement system can promote the progression of interstitial pulmonary fibrosis. In addition, C1q has also demonstrated to exert a tumor-promoting effect in many tumors. However, the role of C1q in idiopathic pulmonary fibrosis and lung cancer still remain unclear.

METHODS: We selected common differentially expressed genes in IPF and non-small cell lung cancer using datasets from GEO, and investigated common hub gene. The hub genes were validated in IPF by establishing mouse model of IPF and using another four datasets from the GEO. Multiple databases were analyzed including those of Kaplan-Meier Plotter, Tumor Immune Estimation Resource (TIMER2.0) and the Human Protein Atlas (HPA) for NSCLC.

RESULTS: In this study, 37 common DEGs were identified in IPF and NSCLC including 32 up-regulated genes and 5 down-regulated genes, and C1q was identified as common hub gene. The methylation status of C1q decreased and the expression levels of C1q increased in both lung cancer and idiopathic pulmonary fibrosis. The prognosis of non-small cell lung cancer and IPF patients with high levels of C1q is poor.

CONCLUSIONS: These results show that C1q participates in pulmonary fibrosis and non-small cell lung cancer, and may be a potential diagnostic / prognostic biomarker or a therapeutic target.

PMID:35078421 | DOI:10.1186/s12885-021-08912-3

Respiration. 2022 Jan 25:1-13. doi: 10.1159/000520657. Online ahead of print.

ABSTRACT

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability.

PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed.

RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis.

CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

PMID:35078193 | DOI:10.1159/000520657

Respiration. 2022 Jan 25:1-8. doi: 10.1159/000521138. Online ahead of print.

ABSTRACT

BACKGROUND: The FIBRONET study was an observational study of patients with idiopathic pulmonary fibrosis (IPF) in Italy.

OBJECTIVES: In this post hoc descriptive analysis, we describe changes in lung function, anxiety/depression, coughing, exacerbations, and adverse events (AEs) in patients receiving nintedanib treatment.

METHODS: Patients with IPF from 20 centers in Italy, aged ≥40 years who received nintedanib for ≥7 months, were followed up for 12 months from study enrollment, attending clinic visits every 3 months. Outcomes included change in forced vital capacity (FVC)% predicted from baseline to 12 months, anxiety/depression measured by the Hospital Anxiety and Depression Scale (HADS), and the proportion of patients with cough, AEs, and exacerbations.

RESULTS: In total, 52 patients received nintedanib (mean duration of 11.6 months). Ten patients had dose reductions from 150 mg to 100 mg twice daily, due to AEs. FVC% predicted was unchanged in the overall nintedanib population (78.7% at baseline; 79.8% at 12 months) and those with a reduced dose (77.7% at baseline; 81.0% at 12 months). HADS score was low at baseline and throughout the study. The proportion of patients with cough decreased from 50.0% to 21.2% over 12 months. Two patients experienced exacerbations, 2 patients discontinued treatment, and 27 (51.9%) reported AEs. The most common AE was diarrhea (34.6%).

CONCLUSIONS: In patients with IPF who received nintedanib in the FIBRONET study, FVC% predicted was stable over 12 months, and the proportion of patients with cough decreased. The safety profile was consistent with the known safety profile for nintedanib in IPF.

PMID:35078170 | DOI:10.1159/000521138

Am J Respir Crit Care Med. 2022 Jan 25. doi: 10.1164/rccm.202110-2244ED. Online ahead of print.

NO ABSTRACT

PMID:35077663 | DOI:10.1164/rccm.202110-2244ED

IEEE Trans Biomed Eng. 2022 Jan 25;PP. doi: 10.1109/TBME.2022.3145688. Online ahead of print.

ABSTRACT

An ability to extract detailed spirometry-like breathing waveforms from wearable sensors promises to greatly improve respiratory health monitoring. Photoplethysmography (PPG) has been researched in depth for estimation of respiration rate, given that it varies with respiration through overall intensity, pulse amplitude and pulse interval. We compare and contrast the extraction of these three respiratory modes from both the ear canal and finger and show a marked improvement in the respiratory power for respiration induced intensity variations and pulse amplitude variations when recording from the ear canal. We next employ a data driven multi-scale method, noise assisted multivariate empirical mode decomposition (NA-MEMD), which allows for simultaneous analysis of all three respiratory modes to extract detailed respiratory waveforms from in-ear PPG. For rigour, we considered in-ear PPG recordings from healthy subjects, both older and young, patients with chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF) and healthy subjects with artificially obstructed breathing. Specific in-ear PPG waveform changes are observed for COPD, such as a decreased inspiratory duty cycle and an increased inspiratory magnitude, when compared with expiratory magnitude. These differences are used to classify COPD from healthy and IPF waveforms with a sensitivity of 87% and an overall accuracy of 92%. Our findings indicate the promise of in-ear PPG for COPD screening and unobtrusive respiratory monitoring in ambulatory scenarios and in consumer wearables.

PMID:35077352 | DOI:10.1109/TBME.2022.3145688