Diagnostic utility of surgical lung biopsies in elderly patients with indeterminate interstitial lung disease

Background and objective

Idiopathic pulmonary fibrosis (IPF) is increasingly diagnosed by clinical and computed tomography (CT) criteria; however, surgical lung biopsy (SLB) may still be required in patients who lack definite CT features of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic interstitial pneumonia (IIP).

Methods

We searched the pathology records of Mayo Clinic for ambulatory patients at least 75 years old, who underwent SLB between 2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical data were extracted from the record.

Results

A total of 55 patients (35 male) were enrolled. Median (interquartile range) age was 77 (76–80) years. Forced vital capacity was 70 (61–76)% and diffusing capacity of the lungs for carbon monoxide was 48 (42–54)% of predicted. In total, 37 (67%) patients had IPF, including 61% of those with HRCT findings inconsistent with UIP. Thirty‐day mortality was 10% and 90‐day mortality was 15%.

Conclusion

The high mortality rate of SLB complicates the risk–benefit analysis in elderly patients with IIP. The expected value of the SLB is probably highest when the HRCT features are inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than UIP.

     

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.     

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality

Background and objective

Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome.

Methods

Patients with prior UCTD‐interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all‐cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features.

Results

One hundred and one UCTD‐ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud’s phenomenon, positive anti‐nuclear antibody (ANA) and non‐specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features.

Conclusion

Current IPAF criteria encompassed the majority of broadly defined UCTD‐ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

     

Is hypothyroidism in idiopathic pleuroparenchymal fibroelastosis a novel lung-thyroid syndrome?

Background

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare type of interstitial pneumonia characterized by fibroelastosis. Patients with IPPFE as well as idiopathic interstitial pneumonia often have autoimmune diseases, which sometimes coincide with hypothyroidism (HypoT). However, there have been no reports on the association between IPPFE and HypoT. The purpose of this study was to evaluate the correlation between IPPFE and HypoT. We also examined the pathological features of the thyroid glands from autopsied cases.

HRCT of fibrosing lung disease

The use of high‐resolution computed tomography (HRCT) has brought increased diagnostic discrimination to the evaluation of lung disease, particularly fibrosing lung diseases. Once the presence of a predominantly fibrosing lung disease has been established on evaluation of a HRCT, a stepwise approach is proposed that can refine the potential HRCT diagnoses from a list of over 100 different interstitial lung diseases to one of only five fibrosing lung diseases. Within the category of the fibrosing lung diseases, the recognition of idiopathic pulmonary fibrosis (IPF) is key. IPF is the most prevalent idiopathic interstitial pneumonia and has a mortality greater than any of the other diffuse lung diseases. Several diagnostic dilemmas are explored including challenges with the recent IPF diagnosis and management guidelines (2011), as well as with the ‘difficult to characterize’ fibrosing diseases such as smoking‐related lung fibrosis, unclassifiable disease and acute exacerbations of fibrosing lung disease.     

肺活检在特发性肺纤维化诊断中的应用

特发性肺纤维化(IPF)是特发性间质性肺疾病中最常见、预后最差的类型。早诊早治是改善患者预后的关键措施。对于胸部高分辨率CT(HRCT)表现不是典型的普通型间质性肺炎(UIP)时,通常需要进行肺活检辅助诊断。外科肺活检可获取到足够的样本,是获得肺组织学样本的金标准。但外科肺活检可能导致IPF患者病情急性加重,甚至死亡。冷冻肺活检可获得较大体积、保存良好的肺组织和较好的诊断率,且患者死亡风险也比外科肺活检更低,因此可能是外科肺活检的替代方案,但仍需要进一步的研究证实。传统的经支气管镜肺活检和经皮穿刺肺活检因其固有的局限性,现基本不应用于IPF临床诊断中。     

Contemporary Concise Review 2022: Interstitial lung disease

• Novel genetic associations for idiopathic pulmonary fibrosis (IPF) risk have been identified. Common genetic variants associated with IPF are also associated with chronic hypersensitivity pneumonitis.
• The characterization of underlying mechanisms, such as pathways involved in myofibroblast differentiation, may reveal targets for future treatments.
• Newly identified circulating biomarkers are associated with disease progression and mortality.
• Deep learning and machine learning may increase accuracy in the interpretation of CT scans.
• Novel treatments have shown benefit in phase 2 clinical trials.
• Hospitalization with COVID-19 is associated with residual lung abnormalities in a substantial number of patients.
• Inequalities exist in delivering and accessing interstitial lung disease specialist care.

     

特发性肺纤维化高分辨CT征象与肺功能的相关性

目的探讨特发性肺纤维化(IPF)患者的螺旋CT表现特征与肺功能的相关性。方法经临床病理证实的28例IPF患者进行吸气后屏气HRCT扫描,并进行肺功能测定,观察IPF的CT征象及其解剖分布,评价CT表现特征与肺功能损害的关系。结果28例IPF均有不同程度的限制性通气功能障碍。肺HRCT扫描出现最多的征象是网格影(92.8%)、蜂窝影(82.6%);磨玻璃影与FEV1、FEV1/FEV轻度负相关,网格影与DLco显著负相关,蜂窝影和CT总评分与FVC、FEV1、TLC和DL-co均具有很好的负相关性。结论螺旋CT能准确反应IPF的病理变化,IPF不同程度的肺功能受损与螺旋CT征象存在相关性。两者相结合有助于预测IPF的进展、预后以及疗效反应。     

Propuesta multidisciplinar respecto al algoritmo diagnóstico de la fibrosis pulmonar idiopática: papel de la criobiopsia transbronquial

The diagnosis of idiopathic pulmonary fibrosis (IPF) is a complex process that requires the multidisciplinary integration of clinical, radiological, and histological variables. Due to its diagnostic yield, surgical lung biopsy has been the recommended procedure for obtaining samples of lung parenchyma, when required. However, given the morbidity and mortality of this technique, alternative techniques which carry a lower risk have been explored. The most important of these is transbronchial cryobiopsy —transbronchial biopsy with a cryoprobe— which is useful for obtaining lung tissue with less comorbidity. Yield may be lower than surgical biopsy, but it is higher than with transbronchial biopsy with standard forceps. This option has been discussed in the recent clinical guidelines for the diagnosis of IPF, but the authors do not go so far as recommend it. The aim of this article, the result of a multidisciplinary discussion forum, is to review current evidence and make proposals for the use of transbronchial cryobiopsy in the diagnosis of IPF.     

阿魏酸钠对特发性肺间质纤维化患者氧化应激及肺功能的影响

目的探讨阿魏酸钠对特发性肺间质纤维化（IPF）患者氧化应激及肺功能的影响。方法36例特发性肺间质纤维化住院患者被随机分为A、B两组，A组为阳性对照组，进行常规治疗，B组为治疗组，在常规治疗基础上给予阿魏酸钠，疗程12周。另选取20例健康体检者为正常对照组。测定IPF患者治疗前后及健康体检者肺总量（TLC）、一氧化碳弥散量（DLCO）以及血浆中丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH—Px）的含量。结果与正常对照组相比，IPF患者体内MDA显著升高，GSH—Px含量显著降低，TLC及DLCO也明显降低（P〈0．01）。应用阿魏酸钠后，B组患者上述指标的改善明显优于A组，差异具有显著性（P〈0．05）。结论氧化应激是引起IPF的原因之一，阿魏酸钠可能通过调节氧化应激水平，改善IPF患者的肺功能。     

Idiopathic pulmonary fibrosis: Diagnosis,epidemiology and natural history

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disorder of unknown aetiology whose diagnosis involves the careful exclusion of secondary causes for pulmonary fibrosis and the presence of a pattern of usual interstitial pneumonia (UIP) at either high‐resolution computed tomography (HRCT) scan or surgical lung biopsy. Despite great efforts made in establishing precise, universally acknowledged diagnostic criteria for IPF, its ascertainment remains a challenge, especially in those individuals presenting with atypical HRCT patterns. With new drugs emerging, establishing a precise diagnosis is becoming a clinically relevant issue. Although regarded as a rare disease, IPF epidemiology is controversial due to studies relying on old data and adopting mixed, incomparable methodologies for cases definition. Overall, the prevalence and incidence appear to be increasing over the last decades, suggesting that in earlier studies they might have been underestimated because of diagnostic uncertainty. IPF is invariably progressive, although its clinical course might greatly vary on an individual basis, with episodes of severe acute respiratory deterioration (acute exacerbations) being unpredictable. A deeper understanding of the mechanisms responsible for an accelerated course of the disease and the identification of biomarkers of progression would lead to a better stratification of the disease, essential for delivering individualized therapeutic strategies.     

Diagnostic disparity of previous and revised American Thoracic Society guidelines for idiopathic pulmonary fibrosis

BACKGROUND:A revised guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) was formulated by the American Thoracic Society (ATS) in 2011 to improve disease diagnosis and provide a simplified algorithm for clinicians. The impact of these revisions on patient classification, however, remain unclear.OBJECTIVE:To examine the concordance between diagnostic guidelines to understand how revisions impact patient classification.METHODS:A cohort of 54 patients with either suspected IPF or a working diagnosis of IPF was evaluated in a retrospective chart review, in which patient data were examined according to previous and revised ATS guidelines. Patient characteristics influencing the fulfillment of diagnostic criteria were compared using one-way ANOVA and χ² tests.RESULTS:Revised and previous guideline criteria for IPF were met in 78% and 83% of patients, respectively. Revised guidelines modified a classification based on previous guidelines in 28% of cases. Fifteen percent of patients meeting previous ATS guidelines failed to meet revised criteria due to a lack of honeycombing on high-resolution computed tomography and the absence of a surgical lung biopsy. Patients failing to meet previous and revised diagnostic criteria for IPF were younger.CONCLUSION:The revised guidelines for the diagnosis of IPF classify a substantial proportion of patients differently than the previous guidelines.     

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.     

Fibroelastosis pleuropulmonar: ¿es también una entidad idiopática?

Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that has been recently included in the updated consensus on idiopathic interstitial pneumonias. It shares some clinical features with other chronic interstitial pneumonias (dyspnea, dry cough), and is radiologically characterized by pleural and subpleural parenchymal fibrosis and elastosis, mainly in the upper lobes. The main histological findings include pleural fibrosis and prominent subpleural and parenchymal fibroelastosis. Its characterization is based on the increasing number of cases reported in the literature, so several aspects of the etiology, pathogenesis and natural history are still unknown. Although some cases have been described as idiopathic, PPFE has been reported as a complication after bone marrow transplantation, lung transplantation and chemotherapy, especially with alkylating agents.Spontaneous or iatrogenic pneumothorax is a frequently reported complication of invasive diagnostic tests for identifying PPFE. The disease course is variable, ranging from slow progression to rapid clinical deterioration. No treatment has shown evidence of efficacy, and lung transplantation remains the only option for patients who fulfill the diagnostic criteria for this option. Recognizing and disseminating the specific features of PPFE is essential to raise the level of clinical suspicion for this entity, and to implement appropriate multidisciplinary diagnostic management.     

Lobar distribution of non-emphysematous gas trapping and lung hyperinflation in chronic obstructive pulmonary disease

BackgroundLung hyperinflation in chronic obstructive pulmonary disease (COPD) is closely associated with emphysema and non-emphysematous gas trapping, termed functional small airway disease (fSAD), on inspiratory and expiratory computed tomography (CT). Because the cranial-caudal emphysema distribution affects pulmonary function and fSAD may precede emphysema on CT, we tested the hypothesis that lobar fSAD distribution would affect lung hyperinflation differently in COPD with minimal and established emphysema.MethodsThe volume percentages of fSAD and emphysema (fSAD% and Emph%) over the upper and lower lobes were measured using inspiratory and expiratory CT in 70 subjects with COPD. Subjects were divided into those with minimal and established emphysema (n = 36 and 34) using a threshold of 10% Emph% in the whole lung.ResultsIn the minimal emphysema group, fSAD% in the upper and lower lobes was positively correlated with functional residual capacity (FRC) and residual volume to total lung capacity ratio (RV/TLC), and the correlation of fSAD% with RV/TLC was greater in the lower lobes. Conversely, in the established emphysema group, fSAD% in the upper and lower lobes was correlated with RV/TLC, but not with FRC. In multivariate analysis, fSAD% in the lower lobes, but not in the upper lobes, was associated with RV/TLC in subjects with minimal emphysema after adjusting for age, smoking status, and bronchodilator use.ConclusionNon-emphysematous gas trapping in the upper and lower lobes has a distinct physiological effect, especially in COPD with minimal emphysema. This local evaluation might allow sensitive detection of changes in lung hyperinflation in COPD.     

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。     

Significance of lung shrinkage on CXR as a prognostic factor in patients with idiopathic pulmonary fibrosis

OBJECTIVE: The aim of this study was to determine whether the presence of lung shrinkage on CXR can predict diminished survival in patients with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). METHODOLOGY: In a hospital-based cohort study 68 subjects diagnosed with IPF/UIP by surgical lung biopsy or at autopsy were observed for a mean of 7.6 years. The radiographic scores from Cherniack's method, pulmonary function tests, arterial blood gas, and haematological data were obtained at initial presentation. Longitudinal radiographic changes over a mean interval of 2.7 years were measured. Survival analysis was performed using Kaplan-Meier and Cox's proportional hazards regression analysis. RESULTS: At some point during the observation period 36 (53%) of 68 patients did not exhibit lung shrinkage and 32 (47%) of 68 patients showed lung shrinkage. Patients with lung shrinkage were more likely to have a diminished survival than those with lung preservation; median survival was 4.4 vs 7.8 years, respectively. Lung shrinkage during the observation period (hazard ratio, 3.89; 95% CI = 1.68-9.01; P= 0.001) was associated with lower rates of survival. CONCLUSION: In patients with IPF/UIP, lung shrinkage on CXR during the observation period was a poor prognostic factor.     

Outcomes and safety of surgical lung biopsy for interstitial lung disease

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.     

Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects.MethodsForty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I–IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses.ResultsDiagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility.ConclusionsWe concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone.     

Lung transplantation in IIP: A review

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non‐specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long‐term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post‐transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long‐term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.