Stem Cell Res Ther. 2021 Mar 1;12(1):156. doi: 10.1186/s13287-021-02201-3.

ABSTRACT

BACKGROUND: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments.

METHODS: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration.

RESULTS: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05).

CONCLUSIONS: BMMSC treatment inhibited age-associated lung tissue degeneration.

PMID:33648583 | DOI:10.1186/s13287-021-02201-3

Aging (Albany NY). 2021 Mar 1;13. doi: 10.18632/aging.202725. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. The current coronavirus disease 2019 (COVID-19) shares some similarities with IPF. SARS-CoV-2 related genes have been reported to be broadly regulated by N6-methyladenosine (m6A) RNA modification. Here, we identified the association between m6A methylation regulators, COVID-19 infection pathways, and immune responses in IPF. The characteristic gene expression networks and immune infiltration patterns of m6A-SARS-CoV-2 related genes in different tissues of IPF were revealed. We subsequently evaluated the influence of these related gene expression patterns and immune infiltration patterns on the prognosis/lung function of IPF patients. The IPF cohort was obtained from the Gene Expression Omnibus dataset. Pearson correlation analysis was performed to identify the correlations among genes or cells. The CIBERSORT algorithm was used to assess the infiltration of 22 types of immune cells. The least absolute shrinkage and selection operator (LASSO) and proportional hazards model (Cox model) were used to develop the prognosis prediction model. Our research is pivotal for further understanding of the cellular and genetic links between IPF and SARS-CoV-2 infection in the context of the COVID-19 pandemic, which may contribute to providing new ideas for prognosis assessment and treatment of both diseases.

PMID:33647885 | DOI:10.18632/aging.202725

ANZ J Surg. 2021 Feb 28. doi: 10.1111/ans.16681. Online ahead of print.

ABSTRACT

BACKGROUND: Histology represents the major source of information to define a usual interstitial pneumonia (UIP) pattern. However, the procedure is associated with significant morbidity and mortality. The aim of this study was to evaluate morbidity and mortality of surgical lung biopsy (SLB) in diagnosing UIP.

METHODS: Patients undergoing SLB with the ultimate diagnosis of UIP were studied. Clinical data concerning medical history, histology, pulmonary functions, radiology, length of hospital stay (LOS), morbidity and mortality status were retrospectively recruited from four hospitals.

RESULTS: The study included consecutive 93 patients with a SLB diagnosis of UIP. Mean age was 61 ± 8 years, with one third of the patients were ≥65 years. In 58 cases (62.4%), the biopsy was performed by video-assisted thoracoscopic surgery, in 35 (37.7%) by limited thoracotomy. Eighty patients (86%) had possible UIP, 12 (12.9%) had inconsistent with UIP and one (1.1%) had UIP pattern on high-resolution computed tomography. The mean LOS was 5.47 ± 3.16 days. LOS was associated with smoking status (P = 0.024), type of biopsy (P = 0.00), 6-min walk test (P = 0.00) and number of biopsy (P = 0.00). There was no in-hospital and 30-day mortality in our cohort, and 90-day mortality rate was 1.1%. In seven patients (7.5%), we observed postoperative morbidities, predominantly prolonged air leakage (7.5% of all cases). Postoperative morbidity was only associated with the type of SLB. Patients with limited thoracotomy showed greater morbidity rates (17.1% versus 1.7%, P = 0.011).

CONCLUSION: SLB is a relatively safe procedure in the diagnosis of UIP and can be performed in suitable patients with suspected UIP/idiopathic pulmonary fibrosis.

PMID:33645001 | DOI:10.1111/ans.16681

Front Immunol. 2021 Feb 12;11:604602. doi: 10.3389/fimmu.2020.604602. eCollection 2020.

ABSTRACT

Patients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V α1(V) and α2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with α1(V) chain (anti-ColV IgG/ads-α1(V)) and α2(V) chain (anti-ColV IgG/ads-α2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-α1(V) (sample in which Col V α1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-α2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the α1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.

PMID:33643291 | PMC:PMC7907509 | DOI:10.3389/fimmu.2020.604602

Orphanet J Rare Dis. 2021 Feb 27;16(1):111. doi: 10.1186/s13023-021-01750-3.

ABSTRACT

BACKGROUND: Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or ≥ 10% in DLco in one year) was investigated.

RESULTS: The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p < 0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or AE.

CONCLUSION: We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

PMID:33639995 | DOI:10.1186/s13023-021-01750-3

FASEB J. 2021 Mar;35(3):e21422. doi: 10.1096/fj.202001160RR.

ABSTRACT

Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients.

PMID:33638895 | DOI:10.1096/fj.202001160RR

J Heart Lung Transplant. 2021 Jan 23:S1053-2498(21)01421-2. doi: 10.1016/j.healun.2021.01.1391. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have reported similarities in long-term outcomes following lung transplantation for connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis (IPF). However, it is unknown whether CTD-ILD patients are at increased risk of primary graft dysfunction (PGD), delays in extubation, or longer index hospitalizations following transplant compared to IPF patients.

METHODS: We performed a multicenter retrospective cohort study of CTD-ILD and IPF patients enrolled in the Lung Transplant Outcomes Group registry who underwent lung transplantation between 2012 and 2018. We utilized mixed effects logistic regression and stratified Cox proportional hazards regression to determine whether CTD-ILD was independently associated with increased risk for grade 3 PGD or delays in post-transplant extubation and hospital discharge compared to IPF.

RESULTS: A total of 32.7% (33/101) of patients with CTD-ILD and 28.9% (145/501) of patients with IPF developed grade 3 PGD 48-72 hours after transplant. There were no significant differences in odds of grade 3 PGD among patients with CTD-ILD compared to those with IPF (adjusted OR 1.12, 95% CI 0.64-1.97, p = 0.69), nor was CTD-ILD independently associated with a longer post-transplant time to extubation (adjusted HR for first extubation 0.87, 95% CI 0.66-1.13, p = 0.30). However, CTD-ILD was independently associated with a longer post-transplant hospital length of stay (median 23 days [IQR 14-35 days] vs17 days [IQR 12-28 days], adjusted HR for hospital discharge 0.68, 95% CI 0.51-0.90, p = 0.008).

CONCLUSION: Patients with CTD-ILD experienced significantly longer postoperative hospitalizations compared to IPF patients without an increased risk of grade 3 PGD.

PMID:33637413 | DOI:10.1016/j.healun.2021.01.1391

Chem Commun (Camb). 2021 Feb 26. doi: 10.1039/d1cc00354b. Online ahead of print.

ABSTRACT

Nintedanib (BIBF1120), a triple angiokinase inhibitor, was first approved for idiopathic pulmonary fibrosis (IPF) therapy and is also efficacious for lung carcinoma, and interstitial lung diseases, far beyond its inhibition of VEGFR/PDGFR/FGFR. We identified tripeptidyl-peptidase 1 (TPP1) as one of the direct targets of nintedanib employing the affinity-based protein profiling (AfBPP) technique. This may be a new mechanism for nintedanib's role different from tyrosine kinase inhibition.

PMID:33634807 | DOI:10.1039/d1cc00354b

Front Med (Lausanne). 2021 Feb 9;8:600626. doi: 10.3389/fmed.2021.600626. eCollection 2021.

ABSTRACT

Cellular senescence due to telomere dysfunction has been hypothesized to play a role in age-associated diseases including idiopathic pulmonary fibrosis (IPF). It has been postulated that paracrine mediators originating from senescent alveolar epithelia signal to surrounding mesenchymal cells and contribute to disease pathogenesis. However, murine models of telomere-induced alveolar epithelial senescence fail to display the canonical senescence-associated secretory phenotype (SASP) that is observed in senescent human cells. In an effort to understand human-specific responses to telomere dysfunction, we modeled telomere dysfunction-induced senescence in a human alveolar epithelial cell line. We hypothesized that this system would enable us to probe for differences in transcriptional and proteomic senescence pathways in vitro and to identify novel secreted protein (secretome) changes that potentially contribute to the pathogenesis of IPF. Following induction of telomere dysfunction, a robust senescence phenotype was observed. RNA-seq analysis of the senescent cells revealed the SASP and comparisons to previous murine data highlighted differences in response to telomere dysfunction. We conducted a proteomic analysis of the senescent cells using a novel biotin ligase capable of labeling secreted proteins. Candidate biomarkers selected from our transcriptional and secretome data were then evaluated in IPF and control patient plasma. Four novel proteins were found to be differentially expressed between the patient groups: stanniocalcin-1, contactin-1, tenascin C, and total inhibin. Our data show that human telomere-induced, alveolar epithelial senescence results in a transcriptional SASP that is distinct from that seen in analogous murine cells. Our findings suggest that studies in animal models should be carefully validated given the possibility of species-specific responses to telomere dysfunction. We also describe a pragmatic approach for the study of the consequences of telomere-induced alveolar epithelial cell senescence in humans.

PMID:33634147 | PMC:PMC7902064 | DOI:10.3389/fmed.2021.600626

Stem Cell Res Ther. 2021 Feb 25;12(1):147. doi: 10.1186/s13287-021-02215-x.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related disease with no cure. Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy for IPF treatment. Nevertheless, MSCs derived from patients with IPF (IPF-MSCs) become senescent, thereby reducing their beneficial effects in IPF. MicroRNAs (miRNAs) mediate the senescence of MSCs, but the underlying mechanisms are not fully understood. We investigated the mechanisms by which miR-199a-5p regulates IPF-MSC senescence and whether its inhibition could rejuvenate IPF-MSCs and enhance their therapeutic efficacy.

METHODS: Control-MSCs and IPF-MSCs were isolated from the adipose tissue of age-matched healthy and IPF donors, respectively. Cell senescence was examined by senescence-associated β-galactosidase (SA-β-gal) staining. The level of miR-199a-5p was measured by RT-PCR. Autophagy was determined using a transmission electron microscope (TEM). The therapeutic efficacy of anti-miR-199a-5p-IPF-MSCs was assessed using a mouse model of bleomycin-induced lung fibrosis.

RESULTS: Despite similar surface makers, IPF-MSCs exhibited increased cellular senescence and decreased proliferative capacity compared with control-MSCs. The expression of miR-199a-5p was significantly enhanced in the serum of IPF patients and IPF-MSCs compared with that of healthy donors and control-MSCs. The upregulation of miR-199a-5p induced senescence of control-MSCs, whereas the downregulation rescued IPF-MSC senescence. Mechanistically, miR-155-5p suppressed autophagy of MSCs via the AMPK signaling pathway by downregulating the expression of Sirtuin 1(Sirt1), resulting in cellular senescence. Accordingly, miR-155-5p inhibition promoted autophagy and ameliorated IPF-MSC senescence by activating the Sirt1/AMPK signaling pathway. Compared with IPF-MSCs, the transplantation of anti-miR-199a-5p-IPF-MSCs increased the ability to prevent progression of pulmonary fibrosis in bleomycin-treated mice.

CONCLUSIONS: Our study shows that miR-199a-5p regulates MSC senescence in patients with IPF by regulating the Sirt1/AMPK signaling pathway and miR-199a-5p is a novel target to rejuvenate IPF-MSCs and enhance their beneficial effects.

PMID:33632305 | DOI:10.1186/s13287-021-02215-x

Intern Med J. 2021 Feb;51(2):276-279. doi: 10.1111/imj.15191.

ABSTRACT

During 106 865 person-years of follow up, 17 (1.3%) Fremantle Diabetes Study Phase I participants with Type 2 diabetes and 57 (1.1%) matched individuals without diabetes developed idiopathic pulmonary fibrosis (IPF), an incidence rate ratio (95% confidence interval) of 1.40 (0.76-2.44) (P = 0.22). In the diabetes cohort, age at diabetes diagnosis and total serum cholesterol (inversely) predicted incident IPF in competing risk multivariable models. The incidence of IPF was low in community-based cohorts, regardless of Type 2 diabetes status.

PMID:33631852 | DOI:10.1111/imj.15191

Am Surg. 2021 Feb 25:3134821998686. doi: 10.1177/0003134821998686. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) and gastroesophageal reflux disease (GERD) are undoubtedly related. Even though it is not clear yet which one is the primary disease, they certainly interact increasing each other's severity. Symptoms are unreliable to diagnose GERD in patients with IPF, and objective evaluation with pH monitoring and/or bronchoalveolar lavage analysis is mandatory. Pharmacological treatment with proton pump inhibitors (PPIs) may bring control of IPF in few patients, but PPIs do not control reflux but just change the pH of the gastric refluxate. Surgical therapy based on a fundoplication is safe and effective as it controls any type of reflux, independently from the pH of the gastric refluxate. In patients waiting for lung transplantation (if they can tolerate a laparoscopic operation under general anesthesia), a fundoplication before the operation might block the progression of IPF, while after transplantation it might prevent rejection by preventing the bronchiolitis obliterans syndrome.

PMID:33629881 | DOI:10.1177/0003134821998686

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1399-1409. doi: 10.26355/eurrev_202102_24848.

ABSTRACT

Long noncoding RNAs (lncRNAs) are important participants in biological processes including cell proliferation, differentiation and death, as well as pathogenesis of various diseases. LncRNA differentiation antagonizing non-protein coding RNA (DANCR) is an emerging regulator in cell metabolism and many diseases besides cancers. DANCR is negative in epidermal, osteoblastic and endoderm differentiation, but positive in chondrogenic differentiation of progenitor cells. It is protective for calcification of the ligamentum flavum, stroke, acute myocardial infarction and arterial calcification, but a risk factor for bone loss, fracture healing and idiopathic pulmonary fibrosis. In addition, DANCR is a potential target for improving tissue regeneration. Mechanically, DANCR, a cytoplasmic lncRNA, sponges corresponding microRNAs or interacts with various proteins. This review aims to summarize the role of DANCR in progenitor cells and provide perspectives for further studies.

PMID:33629310 | DOI:10.26355/eurrev_202102_24848

Respir Res. 2021 Feb 24;22(1):66. doi: 10.1186/s12931-021-01643-w.

ABSTRACT

BACKGROUND: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF).

METHODS: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted).

RESULTS: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study.

CONCLUSIONS: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF.

TRIAL REGISTRATION: NCT02803580.

PMID:33627105 | DOI:10.1186/s12931-021-01643-w

Stem Cells Transl Med. 2021 Feb 24. doi: 10.1002/sctm.20-0526. Online ahead of print.

ABSTRACT

Developing, regenerating, and repairing a lung all require interstitial resident fibroblasts (iReFs) to direct the behavior of the epithelial stem cell niche. During lung development, distal lung fibroblasts, in the form of matrix-, myo-, and lipofibroblasts, form the extra cellular matrix (ECM), create tensile strength, and support distal epithelial differentiation, respectively. During de novo septation in a murine pneumonectomy lung regeneration model, developmental processes are reactivated within the iReFs, indicating progenitor function well into adulthood. In contrast to the regenerative activation of fibroblasts upon acute injury, chronic injury results in fibrotic activation. In murine lung fibrosis models, fibroblasts can pathologically differentiate into lineages beyond their normal commitment during homeostasis. In lung injury, recently defined alveolar niche cells support the expansion of alveolar epithelial progenitors to regenerate the epithelium. In human fibrotic lung diseases like bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD), dynamic changes in matrix-, myo-, lipofibroblasts, and alveolar niche cells suggest differential requirements for injury pathogenesis and repair. In this review, we summarize the role of alveolar fibroblasts and their activation stage in alveolar septation and regeneration and incorporate them into the context of human lung disease, discussing fibroblast activation stages and how they contribute to BPD, IPF, and COPD.

PMID:33624948 | DOI:10.1002/sctm.20-0526

Magn Reson Med. 2021 Feb 23. doi: 10.1002/mrm.28703. Online ahead of print.

ABSTRACT

PURPOSE: This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3 He and 129 Xe DWI signals within two micro-CT-derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs.

METHODS: The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro-CT images of excised human lungs and meshed for finite element simulations of the Bloch-Torrey equations. 3 He and 129 Xe multiple b value DWI experiments across a range of diffusion times (3 He Δ = 1.6 ms; 129 Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh's mean linear intercept length, calculated from intercept length measurements within micro-CT segmentation masks.

RESULTS: The SEM-derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3 He (Δ = 1.6 ms) and 129 Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129 Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model-derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129 Xe Δ = 20 ms for both healthy and IPF meshes, respectively.

CONCLUSION: This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

PMID:33624325 | DOI:10.1002/mrm.28703

Thorax. 2021 Feb 23:thoraxjnl-2021-216863. doi: 10.1136/thoraxjnl-2021-216863. Online ahead of print.

NO ABSTRACT

PMID:33622980 | DOI:10.1136/thoraxjnl-2021-216863

Expectations about treatment of idiopathic pulmonary fibrosis: Comparative survey of patients, carers and physicians (the RESPIR French survey).

Respir Med Res. 2021 Jan 05;79:100811

Authors: Cottin V, Bergot E, Bourdin A, Nunes H, Prévot G, Wallaert B, Marchand-Adam S

Abstract
CONTEXT: Idiopathic pulmonary fibrosis (IPF) is a severe chronic disease during which anxiety and depression are frequent comorbidities. Better knowledge of patients' expectations is needed to inform an action plan to improve medical care.
AIM: To describe feelings and expectations of patients suffering from IPF and of their carers about antifibrotic therapy and compare them to what is perceived by their pulmonologist.
METHODS: National prospective study on practices and perceptions. Specific questionnaires were e-mailed to all 3276 pulmonologists in France who, in turn, invited patients and carers to participate in a survey.
RESULTS: 147 pulmonologists, 161 patients and 144 carers participated in the survey. The role of the carer was evaluated as "important" or "very important" by more than 90% of participants, i.e. pulmonologists, patients or carers. Inconsistencies between how patients felt and how pulmonologists perceived them were identified: 88% of patients responded that they understood quite well what IPF is (vs. 75% of patients according to pulmonologists); 85.5% of patients said they were determined to fight the disease (vs. 68.0%); 61.7% of patients wanted to be kept informed of potential complications before they occurred (vs. 69.6%) and 81.2% wanted to be involved in therapeutic decisions (vs. 43.1%). Globally, patients had a more positive view of antifibrotic therapies than expected by pulmonologists: 41.5% evaluated their advantages superior to what they had expected (vs. 29.1% of patients according to pulmonologists) and 76.5% had a positive image of the benefits/disadvantages ratio (vs. 62.4%). Although pulmonologists had the impression that they were keeping their patients well-informed about exacerbations, hospital stays and the possible negative evolution of the disease despite antifibrotic therapies, 34.0%, 42.0% and 22.0% of patients respectively declared not being aware of these aspects.
CONCLUSION: The feelings of patients suffering from IPF regarding their disease and treatment globally proved more positive compared with how pulmonologists perceived them. Taking into account the expectations and needs of patients may allow healthcare professionals to better address their needs and priorities.

PMID: 33618076 [PubMed - as supplied by publisher]

Gene therapy strategies for idiopathic pulmonary fibrosis: recent advances, current challenges, and future directions.

Mol Ther Methods Clin Dev. 2021 Mar 12;20:483-496

Authors: Ruigrok MJR, Frijlink HW, Melgert BN, Olinga P, Hinrichs WLJ

Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic disease in which the lungs become irreversibly scarred, leading to declining lung function. As currently available drugs do not cure IPF, there remains a great medical need for more effective treatments. Perhaps this need could be addressed by gene therapies, which offer powerful and versatile ways to attenuate a wide range of processes involved in fibrosis. Despite the potential benefits of gene therapy, no one has reviewed the current state of knowledge regarding its application for treating IPF. We therefore analyzed publications that reported the use of gene therapies to treat pulmonary fibrosis in animals, as clinical studies have not been published yet. In this review, we first provide an introduction on the pathophysiology of IPF and the most well-established gene therapy approaches. We then present a comprehensive evaluation of published animal studies, after which we provide recommendations for future research to address challenges with respect to the selection and use of animal models as well as the development of delivery vectors and dosage forms. Addressing these considerations will bring gene therapies one step closer to clinical testing and thus closer to patients.

PMID: 33614824 [PubMed]

Cryptogenic organising pneumonia: an unusual cause of pleuritic chest pain.

BMJ Case Rep. 2021 Jan 18;14(1):

Authors: Ceci Bonello R, Ceci Bonello E, Vassallo C, Bellia EG

Abstract
A 76-year-old woman presented with a 2-hour history of pleuritic chest pain with no other associated symptoms. Blood investigations revealed raised inflammatory markers and an elevated white cell count. On chest radiograph, an airspace shadow indicative of a consolidation was prominent. This was followed by a CT scan of her thorax which showed a spiculated lesion in the right upper lobe, a lesion in the posterior segment of the left lower lobe and mildly enlarged right hilar lymph nodes. She was started on dual antibiotic therapy; however, the patient's clinical status and inflammatory markers did not improve. A bronchoscopy was performed which excluded malignancy and atypical pathogens. CT-guided biopsy confirmed the presence of cryptogenic organising pneumonia. Prednisolone 50 mg daily was prescribed with quick resolution of symptoms.

PMID: 33462025 [PubMed - indexed for MEDLINE]