Racial and ethnic disparities in antifibrotic therapy in idiopathic pulmonary fibrosis

Background and Objective

Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis.

Methods

Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired-wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients. Mortality of treated and untreated IPF patients was compared after propensity score matching for age, sex, nicotine dependence, oxygen dependence and predicted FVC. Additional comparisons were performed in subgroups of IPF patients older than 65 years of age and with lower lung function.

Results

Of 47,184 IPF patients identified, the majority were White (35,082), followed by Hispanic (6079), Black (5245) and Asian (1221). When subgroups were submitted to matched cohort pair-wise comparisons, anti-fibrotic usage was lower among Black patients compared to White (6.2% vs. 11.4%, p-value <0.0001), Hispanic (10.8% vs. 20.2%, p-value <0.0001) and Asian patients (9.6% vs. 14.7%, p-value = 0.0006). Similar treatment differences were noted in Black individuals older than 65 years and those with lower lung function. Mortality among White patients, but not Hispanic, Black, or Asian patients, was lower in patients on antifibrotic therapy versus not on therapy.

Conclusion

This study demonstrated that Black IPF patients had lower antifibrotic use compared to White, Hispanic and Asian patients. Our findings suggest that urgent action is needed to understand the reason why racial disparities exist in the treatment of IPF.     

Heart rate recovery after six-minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis

Background and objective: In patients with IPF, we sought to validate that abnormal heart rate recovery at 1 min (HRR1) after six‐minute walk test (6MWT) predicts mortality and to explore the relationship between abnormal HRR1 and pulmonary hypertension (PH). Methods: We identified IPF patients who performed a 6MWT as part of their clinical evaluation between 2006 and 2009 and were followed to lung transplantation or death. Right heart catheterization (RHC) data were collated and analysed for the subgroup who had this procedure. Results: There were 160 subjects who qualified for the survival analysis, and those with an abnormal HRR1 had worse survival than subjects with normal HRR1 (log‐rank P = 0.01). Eighty‐two subjects had a right heart catheter (RHC); among them, abnormal HRR1 was associated with RHC‐confirmed PH (χ² = 4.83, P = 0.03) and had a sensitivity, specificity, positive predictive value and negative predictive value of 52%, 74%, 41% and 82%, respectively, for PH. In bivariate and multivariable analyses, abnormal HRR1 appeared to be the strongest predictor of RHC‐confirmed PH (odds ratio (OR) = 4.0, 95% CI: 1.17–13.69, P = 0.02 in the multivariable analysis). Conclusions: This study adds to data that support the validity of abnormal HRR1 as a predictor of mortality and of RHC‐confirmed PH in IPF. Research is needed to further investigate the link between abnormal HRR1 and PH and to elucidate heart–lung interactions at work during exercise and recovery in patients with IPF.     

特发性肺纤维化的治疗进展

特发性肺纤维化是一种慢性、弥散性肺间质病变,以普通型间质性肺炎为特征性组织学表现。特发性肺纤维化以进行性肺损伤、炎症、肺组织纤维化为特征。糖皮质激素和免疫抑制剂/细胞毒性药物临床效果欠佳,提示炎症并未在肺纤维化中起重要的病理生理作用,研究发现肺泡上皮损伤可以直接导致肺纤维化。目前尚无有效的治疗方案能取得肯定的疗效。因此,新的治疗措施引发了研究者浓厚的兴趣。然而特发性肺纤维化的研究进展缓慢,预后很差,诊断后中期生存率小于3年。本文主要介绍特发性肺纤维化在治疗方面的进展。     

Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV) in idiopathic pulmonary fibrosis

Background and Objective

There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers.

Study Design and Methods

IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CT_PFAV) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CT_PFAV calculated using a Hounsfield-unit (−40 to −200HU) threshold range expressed as a percentage of total lung volume. CT_PFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores.

Results

There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CT_PFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CT_PFAV correlated significantly with DLCO% predicted (R² = 0.356, p < 0.0001) and FVC% predicted (R² = 0.407, p < 0.0001) in patients with IPF. CT_PFAV correlated with CT features of fibrosis; higher CT_PFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CT_PFAV showed no correlation with serum lipids.

Conclusion

CT_PFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CT_PFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.     

Multiple breath washout: A new and promising lung function test for patients with idiopathic pulmonary fibrosis

Background and objective

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease affecting the parenchyma. Nitrogen multiple‐breath washout (N₂‐MBW) is a lung function test that measures ventilation inhomogeneity, a biomarker of small airway disease. We assessed clinical properties of N₂‐MBW in IPF.

Methods

In this prospective cohort pilot study, 25 IPF patients and 25 healthy controls were assessed at baseline and 10 patients at median 6.2 months later. Outcomes included the lung clearance index (LCI) from N₂‐MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the lungs for carbon monoxide (DL_CO), bronchiectasis score from computed tomography scans, the Gender–Age–Physiology (GAP score for IPF) stage and death or lung transplantation (LTx). Study end points were feasibility, repeatability, discriminative capacity and correlation with disease severity and structural lung damage.

Results

All patients were able to perform N₂‐MBW. LCI was repeatable and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1–13.8) in IPF versus 7.3 (6.9–8.4) in controls (P < 0.0001). LCI correlated with DL_CO corrected for haemoglobin (corrDL_CO; r = −0.49, P = 0.016), bronchiectasis score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with FVC. FVC was not related to bronchiectasis. During follow‐up, six patients died and one received LTx. LCI correlated with the latter compound outcome: hazard ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population.

Conclusion

N₂‐MBW is a feasible, reliable and valid lung function test in IPF. LCI correlates with diffusion impairment, structural airway damage and clinical disease severity. LCI is a promising surveillance tool in IPF that may predict mortality.

     

Clinical characteristics of non-idiopathic pulmonary fibrosis,progressive fibrosing interstitial lung diseases: A single-center retrospective study

Progressive fibrosing interstitial lung disease (PF-ILD) is a progressive phenotype of fibrosing ILDs with varying definitions and elusive clinical characteristics. We aimed to clarify the clinical features and prognosis of PF-ILD cases based on the deterioration of pulmonary function.Altogether, 91 consecutive ILD patients who underwent at least 2 pulmonary function tests (PFTs) with an interval of at least 24 months, as the screening period, between January 2009 and December 2015 were retrospectively reviewed. The deterioration of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLco) was calculated based on PFT data and screening period. The definition of PF-ILD was

• 1.relative decline of 10% or more in FVC per 24 months or
• 2.relative decline in FVC of 5% or more with decline in DLco of 15% or more per 24 months.

Medical records of 34 patients with idiopathic pulmonary fibrosis (IPF), 11 patients with non-IPF, PF-ILD, and 46 patients with non-IPF, non-PF-ILD were retrospectively analyzed. Patient characteristics, pharmacologic or non-pharmacologic treatment status, and prognosis were compared between the IPF and non-IPF groups and between the non-IPF, PF-ILD and non-IPF, non-PF-ILD groups.Eleven patients (19.3%) showed a progressive phenotype in the non-IPF group. The pulmonary function data at the first PFT were worse in non-IPF, PF-ILD patients than in non-IPF, non-PF-ILD patients. There were no differences in the proportion of patients who were observed without pharmacologic treatment or of those receiving pharmacologic treatment between the non-IPF, PF-ILD and non-IPF, non-PF-ILD groups. Low %FVC at the first PFT and the usual interstitial pneumonia-like fibrotic pattern on high-resolution computed tomography were risk factors for PF-ILD in the non-IPF group. The mortality in the non-IPF, PF-ILD group was significantly worse than that of the non-IPF, non-PF-ILD group and was as poor as that of the IPF group. Multivariate logistic analysis showed that aging and low %DLco at the first PFT were risk factors for mortality within the non-IPF group.The prognosis of non-IPF, PF-ILD patients was as poor as that of IPF patients. Non-IPF, PF-ILD patients require more intensive treatment before disease progression.     

Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis

Background and objective:   Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.
Methods:   Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.
Results:   Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3–84.4), P  < 0.05) and the total health-related quality of life score (−6.1 (95% CI: −11.7 to −0.5), P  < 0.05).
Conclusions:   Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.     

Serum biomarkers in idiopathic pulmonary fibrosis

Within the group of Idiopathic Interstitial Pneumonias (IIPs), above all Idiopathic Pulmonary Fibrosis (IPF) poses a considerable diagnostic and therapeutic problem. Although genetic profiling indicates that IPF, Non Specific Interstitial Pneumonia (NSIP), and chronic hypersensitivity pneumonitis (HP) are distinctly different diseases, in every day practice these diseases can be difficult to tell apart. Furthermore, treatment of these diseases is notoriously difficult. Serum biomarkers reflect our understanding of the underlying pathogenesis and potentially fulfill a role in establishing a diagnosis, prognosis and therapy. While no single biomarker is currently able to accurately predict the presence or absence of an IIP, a composite of several markers holds promise for the future. Several biomarkers, such as KL-6, surfactant proteins and circulating fibrocytes, appear to contribute to our insight into disease progression and prognosis. It is however uncertain whether these markers give us additional information to common diagnostic tests and their value has as yet to be validated for every day practice. Fortunately, the potential of biomarkers is increasingly recognized and biomarker data are prospectively gathered in current placebo-controlled therapeutic trials.     

特发性肺纤维化的综合诊断进展

特发性肺纤维化是最常见的一种特发性间质性肺炎,组织病理表现为普通型间质性肺炎,临床表现为进行性呼吸困难伴有刺激性干咳,确诊依赖于外科肺活检。但肺活检风险大、费用高,不易被患者接受。近年来研究发现综合HRCT、血清标志物、以及肺功能、支气管肺泡灌洗液等检查,可以对IPF作出早期准确的诊断。本文将从上述几个方面作一介绍。     

辛伐他汀辅助治疗特发性肺纤维化的随机对照研究

目的观察口服辛伐他汀对特发性肺纤维化的辅助治疗效果。方法前瞻性对照试验,依标准纳入60名患者,随机分为两组。常规组采用24个月的常规治疗方案:泼尼松联合N-乙酰半胱氨酸和硫唑嘌呤治疗。辛伐他汀组在采用标准方案的基础上口服辛伐他汀20 mg/d。记录两组患者治疗前和治疗3、6、12、18、24、30、36个月的最大肺活量占预测值百分比(FVC%pred)、一氧化碳弥散量占预测值百分比(DLCO/VA%pred)、第一秒用力呼气容积占预测值百分比(FEV1%pred)、6min步行距离、动脉血氧分压(Pa O2),治疗前以及治疗后6、12个月的HRCT的影像学表现,并监测治疗期间不良反应。结果完成试验的患者常规组有29名,辛伐他汀组有24名。辛伐他汀组FVC%pred仅在治疗第9个月时(80.11±9.23)%高于常规组(74.72±6.34)%,P0.01,其余时间两组无统计学差异;辛伐他汀组DLCO/VA%pred在治疗第12、21、30、36个月时高于常规组,P0.05;两组的FEV1%pred没有统计学差异;辛伐他汀组6min步行距离在治疗第9~33个月时高于常规组,P0.05;辛伐他汀组Pa O2在治疗第6~18个月时高于常规组,P0.05;两组的HRCT影像学表现没有统计学差异,辛伐他汀组36个月存活率(62.5%)高于常规组(34.5%),生存分析两组有统计学差异(P=0.012)。结论口服辛伐他汀不能逆转肺纤维化过程,但能改善肺纤维化患者的肺功能参数和气体交换,提高生活质量,短期内有助于延长患者生命。