Adv Respir Med. 2021 Sep 27. doi: 10.5603/ARM.a2021.0072. Online ahead of print.

ABSTRACT

Nintedanib is an antifibrotic drug that has an inhibitory effect on growth factor tyrosine kinases. In patients with idiopathic pulmonary fibrosis and systemic scleroderma-associated interstitial pneumonia (SSc-IP), nintedanib has been effective in suppressing the decline in forced vital capacity over time and the onset of acute exacerbation of interstitial pneumonia. Here, we report a SSc-IP patient who showed an improvement on CT images following nintedanib treatment. To our knowledge, this is the first report of such a case. Although SSc-IP patients are very rare, additional clinical experience and understanding will be required to prove the therapeutic benefit of nintedanib in these cases in relation to improved chest images.

PMID:34569613 | DOI:10.5603/ARM.a2021.0072

Cureus. 2021 Aug 18;13(8):e17295. doi: 10.7759/cureus.17295. eCollection 2021 Aug.

ABSTRACT

Wegener's granulomatosis, now more commonly referred to as granulomatosis with polyangiitis (GPA), is a rare, idiopathic, systemic inflammatory disease, most commonly involving the respiratory tract, kidneys, and sinonasal region. The condition affects small and medium-sized blood vessels, such as arteries, arterioles, venules, and capillaries. Some cases of the disease presenting as retroperitoneal fibrosis and/or affecting the aorta have been reported. Although advances in the treatment of GPA have contributed to a decline in mortality, early diagnosis is still of vital importance due to the possible complications of the disease. Here, we present the case of a 69-year-old man with acute-onset abdominal pain. Ultrasound of the abdomen showed left-sided hydronephrosis. Computed tomography detected cavitating pulmonary lesions and peri-iliac alterations caused by retroperitoneal fibrosis with involvement of the crossing ureter. Laboratory results revealed high antineutrophil cytoplasmic antibody levels and high inflammatory markers. A lung biopsy performed via bronchoscopy revealed necrotizing granulomas and solidified the diagnosis of GPA both in the lung and the peri-iliac region. Treatment with immunosuppressive agents and glucocorticoids was initiated. A follow-up after two months showed regression of the pulmonary lesions and partial resolution of the hydronephrosis as well as reduced inflammatory markers in the blood tests.

PMID:34567857 | PMC:PMC8451527 | DOI:10.7759/cureus.17295

Turk J Med Sci. 2021 Sep 27. doi: 10.3906/sag-2102-262. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Phase III trials have demonstrated a significant efficacy and an acceptable safety for pirfenidone in patients having mild to moderate idiopathic pulmonary fibrosis (IPF). Real-life data on the use of pirfenidone 200 mg tablets are limited. This study aimed to investigate the efficacy and safety of pirfenidone 200 mg tablets for the treatment of IPF in a real-life setting.

MATERIALS AND METHODS: A retrospective, multicenter study conducted in four university hospitals in XXX between January 2017 and January 2019. Clinical records of patients diagnosed with mild to moderate IPF and receiving pirfenidone (200 mg tablets, total 2400 mg/day) were reviewed retrospectively and consecutively. Pulmonary function measurements including forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) were analyzed at baseline and after 6-month of pirfenidone treatment. Descriptive statistics were expressed as mean, standard error or median (minimum-maximum), number and percentage, where appropriate.

RESULTS: The study included 82 patients, of whom 87.8% were males (mean age, 66 years). After 6-month of treatment, 7 patients discontinued the treatment. Of the remaining 75 patients, 71 (94.6%) remained stable, 4 (5.4%) had progressive disease as evident by a decline in the FVC% of at least 10% while on treatment, and 45 (61.3%) had improved cough. At least one adverse event (AE) associated with the treatment was observed in 28 (37.3%) patients.

CONCLUSION: Pirfenidone 200 mg was effective and well tolerated and associated with relatively mild and manageable AEs in IPF patients.

PMID:34565135 | DOI:10.3906/sag-2102-262

Tomography. 2021 Aug 31;7(3):397-411. doi: 10.3390/tomography7030035.

ABSTRACT

COVID-19 pneumonia represents a challenging health emergency, due to the disproportion between the high transmissibility, morbidity, and mortality of the virus and healthcare systems possibilities. Literature has mainly focused on COVID-19 pneumonia clinical-radiological diagnosis and therapy, and on the most common differential diagnoses, while few papers investigated rare COVID-19 pneumonia differential diagnoses or the overlapping of COVID-19 pneumonia on pre-existing lung pathologies. This article presents the main radiological characteristics of COVID-19 pneumonia and Idiopathic Interstitial Pneumonias (IIPs) to identify key radiological features for a differential diagnosis among IIPs, and between IIPs and COVID-19 pneumonia. COVID-19 pneumonia differential diagnosis with IIPs is challenging, since these entities may share common radiological findings as ground glass opacities, crazy paving patterns, and consolidations. Multidisciplinary discussion is crucial to reach a final and correct diagnosis. Radiologists have a pivotal role in identifying COVID-19 pneumonia patterns, reporting possible overlapping with long-lasting lung diseases, and suggesting potential differential diagnoses. An optimal evaluation of HRTC may help in containing the disease, in promoting better treatment for patients, and in providing an efficient allocation of human and economic resources.

PMID:34564297 | DOI:10.3390/tomography7030035

Toxics. 2021 Aug 30;9(9):204. doi: 10.3390/toxics9090204.

ABSTRACT

The biomonitoring of nanoparticles in patients' broncho-alveolar lavages (BAL) could allow getting insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Our objective was to investigate the relationship between the biomonitoring of nanoparticles in BAL, interstitial lung diseases and occupational exposure to these particles released unintentionally. We analyzed data from a cohort of 100 patients suffering from lung diseases (NanoPI clinical trial, ClinicalTrials.gov Identifier: NCT02549248) and observed that most of the patients showed a high probability of exposure to airborne unintentionally released nanoparticles (>50%), suggesting a potential role of inhaled nanoparticles in lung physiopathology. Depending on the respiratory disease, the amount of patients likely exposed to unintentionally released nanoparticles was variable (e.g., from 88% for idiopathic pulmonary fibrosis to 54% for sarcoidosis). These findings are consistent with the previously performed mineralogical analyses of BAL samples that suggested (i) a role of titanium nanoparticles in idiopathic pulmonary fibrosis and (ii) a contribution of silica submicron particles to sarcoidosis. Further investigations are necessary to draw firm conclusions but these first results strengthen the array of presumptions on the contribution of some inhaled particles (from nano to submicron size) to some idiopathic lung diseases.

PMID:34564355 | DOI:10.3390/toxics9090204

Tomography. 2021 Sep 15;7(3):452-465. doi: 10.3390/tomography7030039.

ABSTRACT

Idiopathic pulmonary fibrosis, a pattern of interstitial lung disease, is often clinically unpredictable in its progression. This paper presents hyperpolarized Xenon-129 chemical shift imaging as a noninvasive, nonradioactive method of probing lung physiology as well as anatomy to monitor subtle changes in subjects with IPF. Twenty subjects, nine healthy and eleven IPF, underwent HP Xe-129 ventilation MRI and 3D-SBCSI. Spirometry was performed on all subjects before imaging, and DLCO and hematocrit were measured in IPF subjects after imaging. Images were post-processed in MATLAB and segmented using ANTs. IPF subjects exhibited, on average, higher Tissue/Gas ratios and lower RBC/Gas ratios compared with healthy subjects, and quantitative maps were more heterogeneous in IPF subjects. The higher ratios are likely due to fibrosis and thickening of the pulmonary interstitium. T2* relaxation was longer in IPF subjects and corresponded with hematocrit scores, although the mechanism is not well understood. A lower chemical shift in the red blood cell spectroscopic peak correlated well with a higher Tissue/RBC ratio and may be explained by reduced blood oxygenation. Tissue/RBC also correlated well, spatially, with areas of fibrosis in HRCT images. These results may help us understand the underlying mechanism behind gas exchange impairment and disease progression.

PMID:34564301 | DOI:10.3390/tomography7030039

BMC Complement Med Ther. 2021 Sep 25;21(1):240. doi: 10.1186/s12906-021-03409-9.

ABSTRACT

BACKGROUND: As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CISCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CISCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms.

METHODS: Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CISCFE-L, -M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CISCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/β-catenin pathway.

RESULTS: CISCFE inhibited the proliferation of MRC-5 cells (IC50: 2.723 ± 0.488 μg/mL) and A549 cells (IC50: 2.235 ± 0.229 μg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-β-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and - 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CISCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes.

CONCLUSION: These findings showed that CISCFE could inhibit IPF development by activating the Wnt/β-catenin pathway and may serve as a treatment for IPF after further investigation.

PMID:34563177 | DOI:10.1186/s12906-021-03409-9

Chin Med J (Engl). 2021 Sep 22. doi: 10.1097/CM9.0000000000001633. Online ahead of print.

NO ABSTRACT

PMID:34561322 | DOI:10.1097/CM9.0000000000001633

Eur Respir J. 2021 Sep 24:2100864. doi: 10.1183/13993003.00864-2021. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies have impelled researchers to reconsider the importance of choice for animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution.This study aimed to follow the dynamic fibrotic features of BLM (Bleomycin)-treated mouse lungs with extended durations through a combination of the latest technologies (micro-CT imaging and histological detection of degraded collagens) with traditional methods. In addition, we also applied immunohistochemistry to explore the distribution of all hydroxyproline-containing molecules.As determined by classical biochemical method, total lung hydroxyproline contents reached peak at 4-week after bleomycin injury and maintained a steady high level thereafter until the end of the experiments (16-week). This result seemed to partially contradict with the changes of other fibrosis evaluation parameters, which indicated a gradual degradation of collagens and a recovery of lung aeration post the fibrosis peak. This inconsistency was well reconciled by our data from immunostaining against hydroxyproline and a fluorescent peptide staining against degraded collagen, together showing large amounts of hydroxyproline-rich degraded collagen fragments detained and enriched within the intracellular regions at 10- or 16-week, rather than at 4-week post the BLM-treatment. Hence, our present data not only offer respiratory researchers a new perspective towards the resolution nature of mouse lung fibrosis, but also remind them to be cautious while using hydroxyproline content assay to evaluate the severity of fibrosis.

PMID:34561295 | DOI:10.1183/13993003.00864-2021

Phys Med Biol. 2021 Sep 24. doi: 10.1088/1361-6560/ac29ce. Online ahead of print.

ABSTRACT

BACKGROUND: Lung compliance is the ability of the lung to expand with changes in pressure and is one of the earliest physiological measurements to be altered in patients with parenchymal lung disease. Therefore, compliance monitoring could potentially identify patients at risk for disease progression. However, in clinical practice, compliance measurements are prohibitively invasive for use as a routine monitoring tool.

PURPOSE: We propose a novel method for computing dynamic lung compliance imaging (LCI) from non-contrast computed tomography (CT) scans. LCI applies image processing methods to free-breathing 4DCT images, acquired under two different continuous positive airway pressures (CPAP) applied using a full-face mask, in order to compute the lung volume change induced by the pressure change. LCI provides a quantitative volumetric map of lung stiffness.

METHODS: We compared mean LCI values computed for 10 patients with idiopathic pulmonary fibrosis (IPF) and 7 non-IPF patients who were screened for lung nodules. 4DCTs were acquired for each patient at 5cm and 10 cm H20 CPAP, as the patients were free breathing at functional residual capacity. LCI was computed from the two 4DCTs. Mean LCI intensities, which represent relative voxel volume change induced by the change in CPAP pressure, were computed.

RESULTS: The mean LCI values for patients with IPF ranged between [0.0309, 0.1165], whereas the values ranged between [0.0704, 0.2185] for the lung nodule cohort. Two-sided Wilcoxon rank sum test indicated that the difference in medians is statistically significant (p value = 0.009) and that LCI -measured compliance is overall lower in the IPF patient cohort.

CONCLUSION: There is considerable difference in lung compliance scores between patients with IPF compared to controls. Future longitudinal studies should look for LC alterations in areas of lung prior to radiographic detection of fibrosis to further characterize LCI's potential utility as an image marker for disease progression.

PMID:34560677 | DOI:10.1088/1361-6560/ac29ce

Int Immunopharmacol. 2021 Sep 21;100:108165. doi: 10.1016/j.intimp.2021.108165. Online ahead of print.

ABSTRACT

Obstructive sleep apnea (OSA) has been increasingly recognized as a risk factor for idiopathic pulmonary fibrosis (IPF). The intermittent hypoxia (IH) and re-oxygenation of OSA contribute to poor outcomes of IPF, however, the potential mechanism remains unknown. Here, C57BL/6J mice were administered intratracheal injection of Bleomycin (BLM) or saline and then exposed to IH (alternating cycles of FiO2 21% for 60S and FiO2 10% for 30 s, 40 cycles/hour, 8 h/day) to mimic OSA or intermittent air (IA) for 4 days, 8 days or 21 days. This study found that pulmonary fibrosis in BLM + IH treated mice was more severe than that in BLM + IA group at day 8 and 21, but not observed at day 4. Besides, the expression of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α),which are related to hypoxia reduced oxidative stress and inflammation, were higher in BLM + IH treated mice than BLM + IA mice, and IH increased these indexes in BLM treated mice from day 4 to day 21. Interestingly, a positive linear correlation between the HIF-1α expression and hydroxyproline (HYP) content was observed. We further found some inflammatory cells in bronchoalveolar lavage fluid were increased significantly from day 4 to 21, and there was a positive correlation between inflammation and ROS expression. Our results demonstrated that IH aggravated BLM-induced pulmonary fibrosis, and ROS/HIF-1α related oxidative stress and inflammation involved. The increase of ROS/HIF-1α related oxidative stress and inflammation may be a potential mechanism of moderate-to-severe OSA in potentiating pulmonary fibrosis of IPF, which warrants further study.

PMID:34560512 | DOI:10.1016/j.intimp.2021.108165

Respir Med. 2021 Sep 16;188:106612. doi: 10.1016/j.rmed.2021.106612. Online ahead of print.

ABSTRACT

PURPOSE: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD.

METHODS: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients.

RESULTS: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis.

CONCLUSION: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis.

PMID:34560351 | DOI:10.1016/j.rmed.2021.106612

Cochrane Database Syst Rev. 2021 Feb 1;2:CD006322. doi: 10.1002/14651858.CD006322.pub4.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is characterised by reduced functional capacity, dyspnoea and exercise-induced hypoxia. Pulmonary rehabilitation is often used to improve symptoms, health-related quality of life and functional status in other chronic lung conditions. There is accumulating evidence for comparable effects of pulmonary rehabilitation in people with ILD. However, further information is needed to clarify the long-term benefit and to strengthen the rationale for pulmonary rehabilitation to be incorporated into standard clinical management of people with ILD. This review updates the results reported in 2014.

OBJECTIVES: To determine whether pulmonary rehabilitation in people with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in people with ILD. To assess the safety of pulmonary rehabilitation in people with ILD.

SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and PEDro from inception to April 2020. We searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts to look for qualifying studies.

SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised controlled trials in which pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in people with ILD of any origin.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. We contacted study authors to request missing data and information regarding adverse effects. We specified a priori subgroup analyses for participants with idiopathic pulmonary fibrosis (IPF) and participants with severe lung disease (low diffusing capacity or desaturation during exercise). There were insufficient data to perform the prespecified subgroup analysis for type of exercise training modality.

MAIN RESULTS: For this update, we included an additional 12 studies resulting in a total of 21 studies. We included 16 studies in the meta-analysis (356 participants undertook pulmonary rehabilitation and 319 were control participants). The mean age of participants ranged from 36 to 72 years and included people with ILD of varying aetiology, sarcoidosis or IPF (with mean transfer factor of carbon dioxide (TLCO) % predicted ranging from 37% to 63%). Most pulmonary rehabilitation programmes were conducted in an outpatient setting, with a small number conducted in home-based, inpatient or tele-rehabilitation settings. The duration of pulmonary rehabilitation ranged from three to 48 weeks. There was a moderate risk of bias due to the absence of outcome assessor blinding and intention-to-treat analyses and the inadequate reporting of randomisation and allocation procedures in 60% of the studies. Pulmonary rehabilitation probably improves the six-minute walk distance (6MWD) with mean difference (MD) of 40.07 metres, 95% confidence interval (CI) 32.70 to 47.44; 585 participants; moderate-certainty evidence). There may be improvements in peak workload (MD 9.04 watts, 95% CI 6.07 to 12.0; 159 participants; low-certainty evidence), peak oxygen consumption (MD 1.28 mL/kg/minute, 95% CI 0.51 to 2.05; 94 participants; low-certainty evidence) and maximum ventilation (MD 7.21 L/minute, 95% CI 4.10 to 10.32; 94 participants; low-certainty evidence). In the subgroup of participants with IPF, there were comparable improvements in 6MWD (MD 37.25 metres, 95% CI 26.16 to 48.33; 278 participants; moderate-certainty evidence), peak workload (MD 9.94 watts, 95% CI 6.39 to 13.49; low-certainty evidence), VO2 (oxygen uptake) peak (MD 1.45 mL/kg/minute, 95% CI 0.51 to 2.40; low-certainty evidence) and maximum ventilation (MD 9.80 L/minute, 95% CI 6.06 to 13.53; 62 participants; low-certainty evidence). The effect of pulmonary rehabilitation on maximum heart rate was uncertain. Pulmonary rehabilitation may reduce dyspnoea in participants with ILD (standardised mean difference (SMD) -0.36, 95% CI -0.58 to -0.14; 348 participants; low-certainty evidence) and in the IPF subgroup (SMD -0.41, 95% CI -0.74 to -0.09; 155 participants; low-certainty evidence). Pulmonary rehabilitation probably improves health-related quality of life: there were improvements in all four domains of the Chronic Respiratory Disease Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) for participants with ILD and for the subgroup of people with IPF. The improvement in SGRQ Total score was -9.29 for participants with ILD (95% CI -11.06 to -7.52; 478 participants; moderate-certainty evidence) and -7.91 for participants with IPF (95% CI -10.55 to -5.26; 194 participants; moderate-certainty evidence). Five studies reported longer-term outcomes, with improvements in exercise capacity, dyspnoea and health-related quality of life still evident six to 12 months following the intervention period (6MWD: MD 32.43, 95% CI 15.58 to 49.28; 297 participants; moderate-certainty evidence; dyspnoea: MD -0.29, 95% CI -0.49 to -0.10; 335 participants; SGRQ Total score: MD -4.93, 95% CI -7.81 to -2.06; 240 participants; low-certainty evidence). In the subgroup of participants with IPF, there were improvements at six to 12 months following the intervention for dyspnoea and SGRQ Impact score. The effect of pulmonary rehabilitation on survival at long-term follow-up is uncertain. There were insufficient data to allow examination of the impact of disease severity or exercise training modality. Ten studies provided information on adverse events; however, there were no adverse events reported during rehabilitation. Four studies reported the death of one pulmonary rehabilitation participant; however, all four studies indicated this death was unrelated to the intervention received.

AUTHORS' CONCLUSIONS: Pulmonary rehabilitation can be performed safely in people with ILD. Pulmonary rehabilitation probably improves functional exercise capacity, dyspnoea and quality of life in the short term, with benefits also probable in IPF. Improvements in functional exercise capacity, dyspnoea and quality of life were sustained longer term. Dyspnoea and quality of life may be sustained in people with IPF. The certainty of evidence was low to moderate, due to inadequate reporting of methods, the lack of outcome assessment blinding and heterogeneity in some results. Further well-designed randomised trials are needed to determine the optimal exercise prescription, and to investigate ways to promote longer-lasting improvements, particularly for people with IPF.

PMID:34559419 | DOI:10.1002/14651858.CD006322.pub4

Indian J Radiol Imaging. 2021 Apr;31(2):480-483. doi: 10.1055/s-0041-1734334. Epub 2021 Jul 28.

ABSTRACT

Idiopathic pulmonary hemosiderosis (IPH) is an unusual cause of pediatric iron deficiency anemia (IDA) characterized by alveolar hemorrhage leading to hemosiderin deposition and fibrosis in the lungs. Though the typical triad of presentation is hemoptysis, IDA, and lung opacities on thoracic radiographs, often the sole manifestation of IPH may be severe IDA in children.

PMID:34556935 | PMC:PMC8448246 | DOI:10.1055/s-0041-1734334

Expert Opin Drug Deliv. 2021 Sep 23. doi: 10.1080/17425247.2021.1985460. Online ahead of print.

ABSTRACT

INTRODUCTION: Nintedanib (NTB) is an orally administered tyrosine kinase inhibitor that has been approved recently by USFDA for idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD). NTB is also prescribed in COVID-19 patients associated with IPF. However, it has an extremely low bioavailability of around 4.7% hence researchers are attempting to address this drawback by different approaches.

AREAS COVERED: The review article focuses on enlisting all the formulation attempts explored by researchers to increase the bioavailability of NTB while also providing meaningful insights into the unexplored areas in formulation development such as targeting the lymphatic system and transdermal delivery. All the patents on the formulation development of NTB have also been summarized.

EXPERT OPINION: NTB has the potential to act on multiple diseases that are still being discovered but, its extremely low bioavailability is a challenge that is to be dealt with for obtaining the full benefit. Few studies have been performed aiming at improving the bioavailability but there are unexplored areas that can be used, a few of which are explained in this article. However, the ability to reproduce laboratory results when scaling up to the industry level is the only factor to be taken into consideration.

PMID:34556001 | DOI:10.1080/17425247.2021.1985460

Am J Respir Crit Care Med. 2021 Sep 23. doi: 10.1164/rccm.202108-2007ED. Online ahead of print.

NO ABSTRACT

PMID:34554892 | DOI:10.1164/rccm.202108-2007ED

Respir Investig. 2021 Sep 18:S2212-5345(21)00144-1. doi: 10.1016/j.resinv.2021.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: The COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD.

METHODS: We retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan-Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used.

RESULTS: The patients' median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10-20), 80 had a high level (21-30), and 23 had a very high level (31-40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161-1.830; p < 0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively.

CONCLUSION: The CAT has prognostic value in FILD.

PMID:34548272 | DOI:10.1016/j.resinv.2021.07.007

Eur J Pharmacol. 2021 Sep 18:174503. doi: 10.1016/j.ejphar.2021.174503. Online ahead of print.

ABSTRACT

Renal fibrosis, a characteristic of all chronic kidney diseases, lacks effective therapeutic drugs currently. Pirfenidone (PFD), a small molecule drug with good oral bioavailability, is widely used in idiopathic pulmonary fibrosis and exerts anti-fibrotic, anti-inflammatory, antioxidant, and anti-apoptotic effects. These effects have been attributed to the suppression of cell growth factors (in particular, but not exclusively, transforming growth factor-β), matrix metalloproteinases, and the epithelial-mesenchymal transition, as well as the possible down-regulation of pro-inflammatory mediators (such as tumour necrosis factor-α), the protection of mitochondrial function, and the regulation of inflammatory cells. Considering the activation of similar anti-fibrotic pathways in lung and kidney disease and the broad activity of PFD, this drug has improved the treatment of the renal fibrotic disease. In this review, we briefly summarise the pharmacokinetics and safety of PFD as well as the mechanisms of PFD focusing on kidney disease. We summarise the effects of PFD on renal function and pathological alterations based on animal experiments, as well as changes in growth factors based on both animal and renal cell experiments. Moreover, given the activation of similar profibrotic pathways in pulmonary diseases and other disorders, we reviewed in-depth the possible signalling pathways targeted by PFD to attenuate renal fibrosis and protect renal function. Finally, we provide an overview of the current clinical trials of PFD for the treatment of renal fibrosis.

PMID:34547247 | DOI:10.1016/j.ejphar.2021.174503

J Comput Assist Tomogr. 2021 Sep-Oct 01;45(5):776-781. doi: 10.1097/RCT.0000000000001230.

ABSTRACT

PURPOSE: A usual interstitial pneumonia (UIP) pattern is common in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of the study was to validate imaging findings differentiating CTD-ILD from IPF in UIP.

METHODS: Patients with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern on computed tomography and/or pathology were included in this study. Prevalence of 3 computed tomography findings shown to be associated with CTD-ILD (the straight edge sign [SES], the exuberant honeycombing sign, and the anterior upper lobe sign [AULS]) were tabulated in CTD-ILD and IPF subjects. The ability of each of these signs to discriminate between CTD-ILD and IPF was evaluated. Survival analysis was also performed using log-rank analysis.

RESULTS: The study cohort included 50 CTD-ILD and 100 IPF subjects with UIP. The SES and the AULS were more common in CTD-ILD than IPF (prevalence, 36.0% and 34.9% in CTD-ILD vs 8.3% and 17.2% in IPF, respectively [P = 0.0105 - <0.001]). The highest specificity (95.7%) of CTD-ILD diagnosis was seen with bilateral SES. Moreover, the SES was associated with improved survival (P = 0.0383), which appeared to be largely because of improvement in survival in IPF subjects. The presence of AULS was associated with pulmonary functional abnormalities.

CONCLUSIONS: A radiographic UIP pattern with evidence of SES or the AULS should raise suspicion for CTD-ILD rather than IPF. Patients with IPF and SES have an attenuated disease course and might represent a different phenotype than those without the SES.

PMID:34546682 | DOI:10.1097/RCT.0000000000001230

JAMA. 2021 Sep 21;326(11):1070-1071. doi: 10.1001/jama.2021.11810.

NO ABSTRACT

PMID:34546305 | DOI:10.1001/jama.2021.11810