Molecules. 2021 Jul 26;26(15):4491. doi: 10.3390/molecules26154491.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with multiple causes, characterized by excessive myofibrocyte aggregation and extracellular matrix deposition. Related studies have shown that transforming growth factor-β1 (TGF-β1) is a key cytokine causing fibrosis, promoting abnormal epithelial-mesenchymal communication and fibroblast-to-myofibroblast transition. Fedratinib (Fed) is a marketed drug for the treatment of primary and secondary myelofibrosis, targeting selective JAK2 tyrosine kinase inhibitors. However, its role in pulmonary fibrosis remains unclear. In this study, we investigated the potential effects and mechanisms of Fed on pulmonary fibrosis in vitro and in vivo. In vitro studies have shown that Fed attenuates TGF-β1- and IL-6-induced myofibroblast activation and inflammatory response by regulating the JAK2/STAT3 signaling pathway. In vivo studies have shown that Fed can reduce bleomycin-induced inflammation and collagen deposition and improve lung function. In conclusion, Fed inhibited inflammation and fibrosis processes induced by TGF-β1 and IL-6 by targeting the JAK2 receptor.

PMID:34361644 | DOI:10.3390/molecules26154491

Int J Mol Sci. 2021 Aug 3;22(15):8335. doi: 10.3390/ijms22158335.

ABSTRACT

Adaptive responses to hypoxia are involved in the progression of lung cancer and pulmonary fibrosis. However, it has not been pointed out that hypoxia may be the link between these diseases. As tumors or scars expand, a lack of oxygen results in the activation of the hypoxia response, promoting cell survival even during chronic conditions. The role of hypoxia-inducible factors (HIFs) as master regulators of this adaptation is crucial in both lung cancer and idiopathic pulmonary fibrosis, which have shown the active transcriptional signature of this pathway. Emerging evidence suggests that interconnected feedback loops such as metabolic changes, fibroblast differentiation or extracellular matrix remodeling contribute to HIF overactivation, making it an irreversible phenomenon. This review will focus on the role of HIF signaling and its possible overlapping in order to identify new opportunities in therapy and regeneration.

PMID:34361103 | DOI:10.3390/ijms22158335

Int J Mol Sci. 2021 Jul 23;22(15):7870. doi: 10.3390/ijms22157870.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by increased activation of fibroblasts/myofibroblasts. Previous reports have shown that IPF fibroblasts are resistant to apoptosis, but the mechanisms remain unclear. Since inhibition of the mitochondrial permeability transition pore (mPTP) has been implicated in the resistance to apoptosis, in this study, we analyzed the role of mitochondrial function and the mPTP on the apoptosis resistance of IPF fibroblasts under basal conditions and after mitomycin C-induced apoptosis. We measured the release of cytochrome c, mPTP opening, mitochondrial calcium release, oxygen consumption, mitochondrial membrane potential, ADP/ATP ratio, ATP concentration, and mitochondrial morphology. We found that IPF fibroblasts were resistant to mitomycin C-induced apoptosis and that calcium, a well-established activator of mPTP, is decreased as well as the release of pro-apoptotic proteins such as cytochrome c. Likewise, IPF fibroblasts showed decreased mitochondrial function, while mPTP was less sensitive to ionomycin-induced opening. Although IPF fibroblasts did not present changes in the mitochondrial membrane potential, we found a fragmented mitochondrial network with scarce, thinned, and disordered mitochondria with reduced ATP levels. Our findings demonstrate that IPF fibroblasts are resistant to mitomycin C-induced apoptosis and that altered mPTP opening contributes to this resistance. In addition, IPF fibroblasts show mitochondrial dysfunction evidenced by a decrease in respiratory parameters.

PMID:34360637 | DOI:10.3390/ijms22157870

Diagnostics (Basel). 2021 Jul 2;11(7):1202. doi: 10.3390/diagnostics11071202.

ABSTRACT

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age- and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease.

PMID:34359285 | DOI:10.3390/diagnostics11071202

Biomedicines. 2021 Jul 20;9(7):847. doi: 10.3390/biomedicines9070847.

ABSTRACT

Endothelial progenitor cells (EPC), which are key effectors in the physiologic vascular network, have been described as relevant players in autoimmune diseases. We previously showed that EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients. Given that ILD constitutes the main cause of mortality in systemic sclerosis (SSc) patients, we aimed to determine the EPC contribution to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC quantification was performed by flow cytometry on blood from 83 individuals: 21 SSc-ILD+ patients and subjects from comparative groups (20 SSc-ILD- and 21 idiopathic pulmonary fibrosis (IPF) patients and 21 healthy controls (HC)). EPC were considered as CD34+, CD45low, CD309+, and CD133+. A significant increase in EPC frequency was found in SSc-ILD+ patients when compared to HC (p < 0.001). SSc-ILD+ patients exhibited a higher EPC frequency than SSc-ILD- patients (p = 0.012), whereas it was markedly reduced compared to IPF patients (p < 0.001). EPC frequency was higher in males (p = 0.04) and negatively correlated to SSc duration (p = 0.04) in SSc-ILD+ patients. Our results indicate a role of EPC in the processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC frequency may be considered as a biomarker of ILD in SSc patients.

PMID:34356910 | DOI:10.3390/biomedicines9070847

RSC Med Chem. 2021 Jun 2;12(7):1222-1231. doi: 10.1039/d1md00023c. eCollection 2021 Jul 21.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a typical survival time between three to five years. Two drugs, pirfenidone and nintedanib have been approved for the treatment of IPF, but they have limited efficacy. Thus, the development of new drugs to treat IPF is an urgent medical need. In this paper we report the discovery of a series of orally active pyrimidin-4(3H)-one analogs which exhibit potent activity in in vitro assays. Among them, HEC-866 showed promising efficacy in rat IPF models. Since HEC-866 also had good oral bioavailability, a long half-life and favorable long-term safety profiles, it was selected for further clinical evaluation.

PMID:34355186 | PMC:PMC8292985 | DOI:10.1039/d1md00023c

Respir Med Case Rep. 2021 Jul 17;34:101472. doi: 10.1016/j.rmcr.2021.101472. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare progressive interstitial lung disease characterized by declining lung function, worsening dyspnea and poor prognosis with median survival of 3-5 years. IPF predominantly affects people over 60 years, it however has worse prognosis in younger patients with genetic predisposition like short telomere syndrome. Nintedanib, one of two anti-fibrotic therapies approved for IPF treatment has occasional neurological side effects like fatigue, dizziness and headaches. Significant polyneuropathy or motor dysfunction is rarely seen. This case report illustrates a patient who developed quadriparesis following initiation of Nintedanib.

PMID:34354919 | PMC:PMC8321914 | DOI:10.1016/j.rmcr.2021.101472

Sci Rep. 2021 Aug 5;11(1):16345. doi: 10.1038/s41598-021-95929-0.

NO ABSTRACT

PMID:34354229 | DOI:10.1038/s41598-021-95929-0

Ann Palliat Med. 2021 Jul;10(7):7289-7297. doi: 10.21037/apm-21-71.

ABSTRACT

BACKGROUND: The aim of our study is to investigate the impact of the simple breathing exercises (LHP's respiratory rehabilitation for pulmonary fibrosis, LHP's RRPF) on patients with idiopathic pulmonary fibrosis (IPF).

METHODS: (I) The safety and effectiveness of LHP's RRPF were first verified in 20 healthy individuals. (II) A total of 101 patients with IPF administrated in Shanghai Pulmonary Hospital between January 2015 and May 2017 were screened, and 82 cases were randomly assigned to receive a 12-month LHP's RRPF program (exercise group) or usual medical care (control group). Lung function, chest X-ray, 6-minute walk distance (6MWD), quality of life (St. George's Respiratory Questionnaire, SGRQ), and EKG were measured at the 6th and 12th month during the trial.

RESULTS: At the 6th month visit, the exercise group showed improved SGRQ score and lung function parameters (FVC, FEV1, and DLCO). At the 12th months visit, the exercise group had significantly improved SGRQ score, 6MWD, and lung function (FVC, FEV1, and DLCO) compared to the control group (P<0.05). No obvious adverse events occurred in the exercise group. The incidence of acute exacerbation and one-year mortality were 7.69% and 2.56%, respectively in the exercise group, which were lower than those (20.9% and 9.3%, respectively) in the control group.

CONCLUSIONS: LHP's RRPF can delay the pulmonary function decline of patients with IPF and improve their quality of life. This breathing exercise may be an adjunct to pulmonary rehabilitation for IPF.

PMID:34353031 | DOI:10.21037/apm-21-71

Eur Respir Rev. 2021 Aug 3;30(161):210017. doi: 10.1183/16000617.0017-2021. Print 2021 Sep 30.

ABSTRACT

Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.

PMID:34348979 | DOI:10.1183/16000617.0017-2021

Braz J Phys Ther. 2021 Jul 21:S1413-3555(21)00075-7. doi: 10.1016/j.bjpt.2021.06.008. Online ahead of print.

ABSTRACT

BACKGROUND: The idiopathic pulmonary fibrosis-specific version of the St George's Respiratory Questionnaire (SGRQ-I) is a valid tool to assess health-related quality of life in patients with interstitial lung diseases (ILDs).

OBJECTIVE: To translate and cross-culturally adapt the SGRQ-I to Brazilian-Portuguese, and to assess its measurement properties.

METHODS: Phase one consisted of the translation and cross-cultural adaptation of the questionnaire. In phase two, intra- and inter-assessor reliability (intraclass correlation coefficient [ICC]), internal consistency (Cronbach's α), minimal detectable change (MDC), ceiling/floor effects, convergent validity (correlation with SF-36 questionnaire), and discriminative validity (according to clinical characteristics) were investigated.

RESULTS: No significant adaptations were needed during the translation process of the SGRQ-I. In phase two, 30 patients with ILD were included (15 men; age 59 ± 10 years; Forced Vital Capacity 73 [61-80]%predicted). The total score on the SGRQ-I presented excellent intra-assessor (ICC: 0.93; 95%CI: 0.85, 0.97]) and inter-assessor (ICC: 0.88; 95%CI: 0.77, 0.94) agreement. Internal consistency was considered adequate for the domains impact, activity, and total score (0.79<α<0.88) but not for symptoms (α=0.43). MDC was 12.8 points and ceiling/floor effects were found in only 3% of patients. No discriminative validity was observed, but there was adequate convergent validity.

CONCLUSION: The results provide preliminary evidence of adequate measurement properties and validity of the Brazilian-Portuguese version of the SGRQ-I for patients with ILDs.

PMID:34348865 | DOI:10.1016/j.bjpt.2021.06.008

Surg Today. 2021 Aug 4. doi: 10.1007/s00595-021-02343-0. Online ahead of print.

ABSTRACT

Postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease and lung cancer has emerged as a serious problem. Therefore, we need to determine the risk factors for the development of postoperative exacerbation of interstitial pneumonia in this population. There are several subtypes of interstitial lung disease, which may lead to confusion about the treatment of patients with interstitial lung disease and lung cancer. Among the idiopathic forms of interstitial lung disease, we focused on idiopathic pulmonary fibrosis (IPF) and reviewed the surgical treatments used for patients with IPF and lung cancer.

PMID:34347162 | DOI:10.1007/s00595-021-02343-0

Lung. 2021 Aug 4. doi: 10.1007/s00408-021-00463-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Despite the high mortality of acute exacerbations of interstitial lung disease (AE-ILD), there is minimal evidence to guide management decisions. We aimed to assess the feasibility and outcomes of a standardized management protocol for AE-ILD.

METHODS: We performed a retrospective cohort study of patients with AE-ILD admitted to hospital between January 2015 and August 2019. Patients were managed with a standardized protocol including chest computed tomography (CT) at diagnosis, pulse corticosteroid treatment, and a follow-up CT 7 days after corticosteroid pulse. The association between idiopathic pulmonary fibrosis (IPF) versus non-IPF diagnosis and transplant-free survival within 1-year of AE-ILD was assessed using adjusted Cox proportional hazards regression survival analysis. Associations with CT chest improvement 7 days after corticosteroid pulse were secondarily assessed.

RESULTS: 89 patients with AE-ILD were identified. 1-year transplant-free and overall survival were 20.2 and 51.7%, respectively. Protocol adherence to pulse corticosteroids was high (95.5%). A diagnosis of IPF was associated with higher risk of death or transplant at 1-year versus a non-IPF diagnosis [hazard ratio (HR) 2.23, 95% CI 1.19-4.17, p = 0.012]. There were no significant associations with 7-day CT improvement; however, CT improvement was associated with higher transplant-free survival (p = 0.02) and a lower risk of in-hospital mortality (χ2 = 7.06, p = 0.01) on unadjusted analysis.

CONCLUSIONS: IPF is associated with a higher risk of death or transplant at 1-year as compared to a non-IPF diagnosis in patients with AE-ILD managed using a standardized protocol. Improvement on CT chest 7 days after corticosteroid pulse is associated with better survival.

PMID:34347146 | DOI:10.1007/s00408-021-00463-5

Respir Res. 2021 Aug 3;22(1):218. doi: 10.1186/s12931-021-01807-8.

ABSTRACT

INTRODUCTION: Treatments of interstitial lung diseases (ILDs) mainly focus on disease stabilization and relief of symptoms by managing inflammation or suppressing fibrosis by (in part costly) drugs. To highlight economic burden of drug treatment in different ILD-subtypes we assessed cost trends and therewith-associated drivers.

METHODS: Using data from the German, observational HILDA study we estimated adjusted mean medication costs over 36-month intervals using one- and two-part Generalized Estimating Equation (GEE) regression models with a gamma distribution and log link. Next, we determined factors associated with costs.

RESULTS: In Idiopathic pulmonary fibrosis (IPF) mean per capita medication costs increased from €1442 before to €11,000€ at the end of study. In non-IPF subtypes, the increase took place at much lower level. Mean per capita ILD-specific medication costs at the end of the study ranged between €487 (other ILD) and €9142 (IPF). At baseline, higher FVC %predicted values were associated with lower medication costs in IPF (-9%) and sarcoidosis (-1%). During follow up higher comorbidity burden escalated costs in progressive fibrosing ILD (PF-ILD) (+52%), sarcoidosis (+60%) and other ILDs (+24%). The effect of disease duration was not uniform, with cost savings in PF-ILD (-8%) and sarcoidosis (-6%), but increased spending in IPF (+11%).

CONCLUSION: Pharmacological management of ILD, in particular of IPF imposes a substantial economic burden on the healthcare system. Strategies to reduce comorbidity burden and early treatment may reduce the impact of ILDs on the healthcare system.

PMID:34344376 | DOI:10.1186/s12931-021-01807-8

Redox Biol. 2021 Jul 26;46:102082. doi: 10.1016/j.redox.2021.102082. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix in the lung with fibroblast-to-myofibroblast transition, leading to chronically compromising lung function and death. However, very little is known about the metabolic alterations of fibroblasts in IPF, and there is still a lack of pharmaceutical agents to target the metabolic dysregulation. Here we show a glycolysis upregulation and fatty acid oxidation (FAO) downregulation in fibroblasts from fibrotic lung, and perturbation of glycolysis and FAO affects fibroblasts transdifferentiation. In addition, there is a significant accumulation of succinate both in fibrotic lung tissues and myofibroblasts, where succinate dehydrogenase (SDH) operates in reverse by reducing fumarate to succinate. Then succinate contributes to glycolysis upregulation and FAO downregulation by stabilizing HIF-1α, which promotes the development of lung fibrosis. In addition, we identify a near-infrared small molecule dye, IR-780, as a targeting agent which stimulates mild inhibition of succinate dehydrogenase subunit A (SDHA) in fibroblasts, and which inhibits TGF-β1 induced SDH and succinate elevation, then to prevent fibrosis formation and respiratory dysfunction. Further, enhanced cell retention of IR-780 is shown to promote severe inhibition of SDHA in myofibroblasts, which may contribute to excessive ROS generation and selectively induces myofibroblasts to apoptosis, and then therapeutically improves established lung fibrosis in vivo. These findings indicate that targeting metabolic dysregulation has significant implications for therapies aimed at lung fibrosis and succinate dehydrogenase is an exciting new therapeutic target to treat IPF.

PMID:34343908 | DOI:10.1016/j.redox.2021.102082

Respir Med. 2021 Jul 26;187:106551. doi: 10.1016/j.rmed.2021.106551. Online ahead of print.

ABSTRACT

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a fatal event that can occur during the clinical course of idiopathic pulmonary fibrosis (IPF). Although data from clinical trials suggest that the antifibrotic agents pirfenidone and nintedanib might reduce the risk of AE-IPF, the incidence of AE-IPF in patients receiving antifibrotic agents in clinical settings is unclear.

OBJECTIVES: To determine the incidence of AE-IPF in patients receiving antifibrotic agents and compare AE-IPF frequency in patients receiving pirfenidone and nintedanib.

METHODS: We retrospectively reviewed the clinical records of 199 patients with IPF who were started on pirfenidone or nintedanib at our institution during the period from 2009 through 2018. Baseline characteristics, incidence of AE-IPF, and outcome after AE-IPF onset were analyzed.

RESULTS: During the observation period, the 1-, 2-, and 3-year cumulative incidences of AE-IPF were 9.3 %, 22.1 %, and 25.0 %, respectively. The 1-, 2-, and 3-year cumulative incidence rates for AE-IPF in the pirfenidone group and nintedanib group were 5.1 % vs. 18.6 %, 20.4 % vs. 25.2 %, and 22.6 % vs. 29.6 %, respectively. AE-IPF incidence was significantly lower in patients treated with pirfenidone than in those treated with nintedanib (log rank test, P = 0.035). The 3-month survival rate after AE-IPF onset was 61.1 % in the pirfenidone group and 61.5 % in the nintedanib group; thus, outcomes after AE-IPF onset were similar in the 2 groups.

CONCLUSION: The reduction in AE-IPF risk might be greater for pirfenidone than for nintedanib.

PMID:34343721 | DOI:10.1016/j.rmed.2021.106551

Am J Respir Crit Care Med. 2021 Aug 3. doi: 10.1164/rccm.202103-0585OC. Online ahead of print.

ABSTRACT

RATIONALE: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF) it is essential to understand its early pathophysiology so that it can be targeted therapeutically.

OBJECTIVES: Perform three-dimensional (3D) assessment of the IPF lung micro-structure using stereology and multi-resolution computed tomography (CT) imaging.

METHODS: Explanted lungs from IPF patients (n=8) and donor controls (n=8) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random (SUR) samples (n=8/lung) were scanned with microCT for stereological assessment of small airways (number, airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness).

RESULTS: The total number of airways on clinical CT was greater in IPF lungs than control lungs (p<0.01), due to an increase in the wall (p<0.05) and lumen area (p<0.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal (p<0.01) and transitional (p<0.001) bronchioles, and an increase in terminal bronchiole wall area (p<0.001) compared to control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness (p<0.05), and dilated airway lumens (p<0.001) leading to honeycomb cyst formations.

CONCLUSION: This study has important implications for the current thinking on how the lung tissue is remodeled in IPF, and highlights small airways as a potential target to modify IPF outcomes.

PMID:34343057 | DOI:10.1164/rccm.202103-0585OC

Am J Respir Cell Mol Biol. 2021 Aug 3. doi: 10.1165/rcmb.2020-0408OC. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease which leads to significant morbidity and mortality from respiratory failure. The two drugs currently approved for clinical use slow the rate of decline in lung function but have not been shown to halt disease progression or reverse established fibrosis. Thus, new therapeutic targets are needed. Endothelial injury and the resultant vascular permeability are critical components in the response to tissue injury, and are present in patients with IPF. However, it remains unclear how vascular permeability affects lung repair and fibrosis following injury. Lipid mediators such as sphingosine-1-phosphate (S1P) are known to regulate multiple homeostatic processes in the lung including vascular permeability. We demonstrate that endothelial cell (EC) specific deletion of the S1P receptor 1 (S1PR1) in mice (EC-S1pr1-/-) results in increased lung vascular permeability at baseline. Following a low dose intratracheal bleomycin challenge, EC-S1pr1-/- mice had increased and persistent vascular permeability compared to wild-type mice, which was strongly correlated with the amount and localization of resulting pulmonary fibrosis. EC-S1pr1-/- mice also had increased immune cell infiltration and activation of the coagulation cascade within the lung. However, increased circulating S1P ligand in ApoM overexpressing mice was insufficient to protect against bleomycin-induced pulmonary fibrosis. Overall, these data demonstrate that endothelial cell S1PR1 controls vascular permeability in the lung, is associated with changes in immune cell infiltration and extravascular coagulation, and modulates the fibrotic response to lung injury.

PMID:34343038 | DOI:10.1165/rcmb.2020-0408OC

Ann Acad Med Singap. 2021 Jul;50(7):556-565.

ABSTRACT

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality.

METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented.

RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, P<0.001) and a significantly larger proportion with post-tuberculous bronchiectasis (37.0% vs 15.8%, P=0.002). Fifty-five percent of our cohort had a history of haemoptysis. Lower body mass index, presence of chronic obstructive pulmonary disease, ever-smoker status, modified Reiff score, radiological severity and history of exacerbations were risk factors for mortality. Survival was significantly shorter in patients with severe bronchiectasis (BSI>9) compared to those with mild or moderate disease (BSI<9). The hazard ratio for severe disease (BSI>9) compared to mild disease (BSI 0-4) was 14.8 (confidence interval 1.929-114.235, P=0.01).

CONCLUSION: The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

PMID:34342336

Br J Hosp Med (Lond). 2021 Jul 2;82(7):1-14. doi: 10.12968/hmed.2020.0556. Epub 2021 Jul 20.

ABSTRACT

Interstitial lung diseases are a complex group of conditions that cause inflammation and scarring of the lung interstitium. This article discusses the diagnosis and management of common interstitial lung diseases including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue disease associated-interstitial lung disease, sarcoidosis and drug-induced interstitial lung disease. A multidisciplinary approach to diagnosis of interstitial lung disease is the gold standard; key history and examination features, blood panel, pulmonary function tests, high resolution computed tomography imaging, and when required bronchoalveolar lavage and lung biopsy results are discussed to reach a multidisciplinary consensus diagnosis. Advances, including the development of the disease-modifying anti-fibrotic medications nintedanib and pirfenidone, continue to shape the future management of interstitial lung disease. A holistic approach to the care of patients with interstitial lung disease is paramount, as they often have a high symptom burden and considerable palliative care needs.

PMID:34338019 | DOI:10.12968/hmed.2020.0556