Location of Fibroblastic Foci: Does the Lesion You Observe Really Suggest Usual Interstitial Pneumonia?

Fibroblastic foci (FF) are considered important findings of usual interstitial pneumonia (UIP); however, they are not only specific to UIP but also observed in various fibrotic interstitial lung diseases (ILDs). Previous studies have reported the significance of FF comparing UIP with nonspecific interstitial pneumonia (NSIP) or secondary interstitial pneumonia, such as collagen vascular disease-related ILD (CVD-ILD) or fibrotic hypersensitivity pneumonitis (FHP). However, only few studies have mentioned their location, and no reports have shown significant results regarding their location. This study aimed to compare the spatial distribution of FF across various forms of ILDs, based on anatomical location. Among patients who underwent lung transplantation at Kyoto University Hospital between April 1, 2008, and March 31, 2023, those diagnosed with idiopathic pulmonary fibrosis (IPF) (n = 24), idiopathic NSIP (n = 11), CVD-ILD (n = 36), and FHP (n = 12) were included, and 744 slides were obtained. FF were classified into 4 categories: peripheral, such as subpleural/paraseptal; intralobular, along the alveolar wall (aFF); centrilobular (cFF); and distorted or dense fibrotic lesions. The number of total and each location's FF/cm2 were counted, and the percentage of each location's FF was calculated. IPF showed more total FF and peripheral FF than NSIP. FHP had more cFF than CVD (P = .026) and NSIP (P = .018). The dFF was higher in IPF than that in CVD (P = .018) and NSIP (P = .039). The aFF/total FF ratio was higher in CVD than that in FHP (P = .021) and IPF (P < .001). A high cFF/total FF ratio was correlated with FHP versus IPF (P = .032). In conclusion, FF with existing peripheral and distorted/dense fibrosis were more closely related to IPF, whereas cFF were highly correlated with FHP. Moreover, a high aFF/total FF ratio was suggestive of CVD.

Katsuragawa H ，Ito H ，Handa T ，Hamaji M ，Menju T ，Sakamoto R ，Date H ，Haga H ，Yoshizawa A ... -  《-》

Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

Churg A ，Poletti V ，Ravaglia C ，Matej R ，Vasakova MK ，Hornychova H ，Stewart B ，Patel D ，Duarte E ，Gomez Manjarres DC ，Mehta HJ ，Vaszar LT ，Tazelaar H ，Wright JL ... -  《-》

A Low Forced Vital Capacity (FVC)/Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Ratio Increases Clinical Suspicion for Fibrotic Hypersensitivity Pneumonitis (FHP) Over Idiopathic Pulmonary Fibrosis (IPF).

Background and objective Fibrotic Hypersensitivity Pneumonitis (FHP) and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases (ILDs) that are challenging to differentiate with prognostic and therapeutic implications. Clinical observations suggest that patients with FHP may have a lower baseline ratio of forced vital capacity (FVC) to the diffusing capacity of the lung for carbon monoxide (DLCO), or FVC/DLCO (F/D) ratio, than patients with IPF. In light of this, we aimed to determine whether patients with FHP have a significantly lower baseline F/D ratio than patients with IPF. Methods A retrospective chart review was performed at a single academic ILD center. Patients with a probable or definite diagnosis of FHP or IPF were considered for inclusion, while patients with poor-quality pulmonary function tests (PFTs) were excluded. The data collected included demographics, diagnosis modality, FVC and DLCO values within six months of diagnosis, as well as hemoglobin levels within three months of PFTs. Baseline F/D ratios were calculated using each patient's FVC percentage of predicted value divided by the DLCO percentage of predicted value adjusted for hemoglobin when available. One-tailed independent two-sample T-tests were performed. Results Eighty-nine patients met the inclusion criteria: 39 (44%) with FHP and 50 (56%) with IPF. The mean baseline F/D ratio was significantly lower for patients with FHP (M = 1.24, 95% CI: 1.14, 1.33) than for patients with IPF (M = 1.44, 95% CI: 1.31, 1.57, T(87) = 2.23, p = 0.014). A secondary analysis excluding patients with pulmonary hypertension and resting hypoxemia was performed, yielding 72 patients: 32 (44%) with FHP and 40 (56%) with IPF. The mean baseline F/D ratio was significantly lower for patients with FHP (M = 1.22, 95% CI: 1.12, 1.31) compared to patients with IPF (M = 1.37, 95% CI: 1.27, 1.46, T (70) = 2.37, p = 0.01). Conclusions In patients with probable to definite FHP versus IPF, the baseline F/D ratio was significantly lower in patients with FHP, even after excluding patients with coexisting pulmonary hypertension and resting hypoxemia. A lower baseline F/D ratio may be a novel, clinic-ready index to heighten clinical suspicion for FHP compared to IPF. Further larger prospective studies are needed to validate our findings.

Vongvivitpatana TS ，Nambiar AM 《Cureus》

Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response. Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. Among 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP. Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Zheng B ，Marinescu DC ，Hague CJ ，Muller NL ，Murphy D ，Churg A ，Wright JL ，Al-Arnawoot A ，Bilawich AM ，Bourgouin P ，Cox G ，Durand C ，Elliot T ，Ellis J ，Fisher JH ，Fladeland D ，Grant-Orser A ，Goobie GC ，Guenther Z ，Haider E ，Hambly N ，Huynh J ，Johannson KA ，Karjala G ，Khalil N ，Kolb M ，Leipsic J ，Lok SD ，MacIsaac S ，McInnis M ，Manganas H ，Marcoux V ，Mayo J ，Morisset J ，Scallan C ，Sedlic T ，Shapera S ，Sun K ，Tan V ，Wong AW ，Ryerson CJ ... -  《-》

Diagnostic and prognostic implications of family history of fibrotic interstitial lung diseases.

Patients with familial fibrotic interstitial lung disease (ILD) experience worse survival than patients with sporadic disease. Current guidelines do not consider family aggregation or genetic information in the diagnostic algorithm for idiopathic pulmonary fibrosis or other fibrotic ILDs. Better characterizing familial cases could help in diagnostic and treatment decision-making. This retrospective cohort study included 222 patients with fibrotic ILD (104 familial and 118 sporadic) from Bellvitge University Hospital. Clinical, radiological, pulmonary functional tests (PFT), and histological evaluations were performed at diagnosis and follow-up. Telomere shortening and disease-associated variants (DAVs) in telomerase-related genes were analysed in familial patients and sporadic patients with telomeric clinical signs. Primary outcomes were the presence of a UIP histological pattern and disease progression. Patients with idiopathic pulmonary fibrosis (IPF) (52%), fibrotic hypersensitivity pneumonitis (23%), and other fibrotic ILDs (25%) were included. 42% of patients underwent lung biopsy. Patients with family aggregation were younger and less frequently associated comorbidities, male sex, and smoking history. However, usual interstitial pneumonia (UIP) was more frequent on pathology (p = 0.005; OR 3.37), especially in patients with indeterminate or non-UIP radiological patterns. Despite similar PFT results at diagnosis, familial patients were more likely to present with progressive disease (p = 0.001; OR 3.75). Carrying a DAV increased the risk of fibrotic progression in familial and sporadic patients (p = 0.029, OR 5.01). Familial patients diagnosed with different fibrotic ILDs were more likely to exhibit a histological UIP pattern and disease progression than sporadic patients, independent of radiological findings and pulmonary function at diagnosis. Considering the diagnostic likelihood of the histological UIP pattern and disease outcome, the presence of family aggregation would be useful in the decision making of multidisciplinary committees.

Duminy-Luppi D ，Alcaide-Aldeano A ，Planas-Cerezales L ，Bermudo G ，Vicens-Zygmunt V ，Luburich P ，Del Río-Carrero B ，Llatjós R ，Pijuan L ，Escobar I ，Rivas F ，Montes-Worboys A ，Gutiérrez-Rodríguez Y ，Rodríguez-Plaza D ，Padró-Miquel A ，Esteve-Garcia A ，Fernández-Varas B ，Flores C ，Fuentes M ，Dorca J ，Santos S ，Perona R ，Günther A ，Shull J ，Molina-Molina M ... -  《-》