BACKGROUND: Health research bodies recommend patient involvement and engagement in research and healthcare planning, although their implementation is not yet widespread. This deficiency extends to progressive pulmonary fibrosis (PPF), where crucial aspects remain unknown, including causal mechanisms, curative treatments and optimal symptom management. This study addresses these gaps by seeking stakeholders\' perspectives to guide research and treatment directions.
METHODS: A priority-setting partnership was established to explore stakeholders\' priorities in the diagnosis, treatment, management and care of PPF, including idiopathic pulmonary fibrosis which is the archetypal PPF. Stakeholders included people living with PPF, their carers, relatives and healthcare professionals involved in their management.
RESULTS: Through an online open-ended survey, 2542 responses were collected from 638 stakeholders. Thematic analysis identified 48 specific research questions, which were then cross-referenced with academic literature to pinpoint research gaps. Following the evidence check, 44 unanswered questions were shortlisted by 834 stakeholders in a second online survey. Ultimately, a top 10 priority list was established through consensus.The prioritised research questions include (1) improved diagnosis accuracy and timing, (2) development of new treatments, (3) enhanced accuracy in primary care, (4) optimal timing for drug and non-drug interventions, (5) effective cough treatment, (6) early intervention for PPF, (7) improved survival rates, (8) symptom reduction, (9) impact of interventions on life expectancy and (10) new treatments with reduced side effects.
CONCLUSIONS: Stakeholders\' priorities can be summarised into five areas: early diagnosis, drug and non-drug treatments, survival and symptom management. Ideally, these topics should guide funding bodies and health policies.

BACKGROUND: Interstitial lung disease (ILD) is comprised of a heterogeneous group of pulmonary diseases. Oxygen therapy is used in patients with advanced lung disease; however, there are challenges associated with initiation of oxygen therapy specific to individuals with ILD. The key objectives of this study were to create a common understanding of the facilitators and barriers to oxygen therapy for patients with ILD, and healthcare professionals (HCP) caring for patients with ILD.
METHODS: This qualitative study included 1 hour semistructured focus groups/interviews. An iterative and concurrent process was used for data collection and analysis to allow for supplementary development of themes and concepts generated. Data analysis used a three-phase approach: coding, categorising and development of themes.
RESULTS: A total of 20 patients and/or caregivers and 31 HCP took part in 34 focus groups/interviews held over 3 months (November 2022-January 2023). Facilitators to oxygen therapy were identified including support from HCP and support groups, the perseverance and self-advocacy of patients, a straightforward administrative process and vendors/private industry that expedite access to oxygen therapy. There were also several barriers to accessing oxygen therapy for patients with ILD. The themes identified include rural disparity, testing requirements and qualifying for funding and the need for ILD-specific evidence base for oxygen therapy.
CONCLUSIONS: Further research is needed to facilitate development of specific exertional oxygen criteria for patients with ILD, to create supports for oxygen use and monitoring and to enable providers to tailor therapy to patients. Oxygen therapy education for ILD should address the benefits and risks of oxygen therapy.

BACKGROUND: Not all chronic diseases have clear pathways and time targets for diagnosis. We explored pathways and timings for four major chronic respiratory diseases in England.
METHODS: Using deidentified electronic healthcare records from Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, we derived cohorts of patients diagnosed with asthma, chronic obstructive pulmonary disease (COPD), ILD or bronchiectasis at three time periods (2008/2009, 2018/2019 and 2020/2021). We followed people 2 years before and 2 years after diagnosis, calculating the proportion of people who presented with symptoms, underwent diagnostic tests, were treated and consulted healthcare (primary or secondary) and calculated time intervals between events. We repeated analyses by socioeconomic status and geographical region.
RESULTS: We descriptively studied patient pathways for 429 619 individuals across all time frames and diseases. Most people (>87%) had first evidence of diagnosis in primary care. The proportion of people reporting symptoms prior to diagnosis was similar for asthma, COPD and ILD (41.0%-57.9%) and higher in bronchiectasis (67.9%-71.8%). The proportion undergoing diagnostic tests was high for COPD and bronchiectasis (77.6%-89.2%) and lower for asthma (14%-32.7%) and ILD (2.6%-3.3%). The proportion of people undergoing diagnostic tests decreased in 2020/2021 for all diseases, mostly COPD. Time (months) (median (IQR)) between symptoms and diagnosis, averaged over three time periods, was lowest in asthma (~7.5 (1.3-16.0)), followed by COPD (~8.6 (1.8-17.2)), ILD (~10.1 (3.6-18.0)) and bronchiectasis (~13.5 (5.9-19.8)). Time from symptoms to diagnosis increased by ~2 months in asthma and COPD over the three time periods. Although most patients were symptomatically treated prior to diagnosis, time between diagnosis and postdiagnostic treatment was around 4 months for ILD, 3 months for bronchiectasis and instantaneous for asthma and COPD. Socioeconomic status and regional trends showed little disparity.
CONCLUSIONS: Current pathways demonstrate missed opportunities to diagnose and manage disease and to improve disease coding.

BACKGROUND: Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available.
RESULTS: This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered.
CONCLUSIONS: There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.

OBJECTIVE: Interstitial fibrosis in papillary thyroid microcarcinoma is a subject which is under-investigated. The aim of this study is to determine the relationship between interstitial fibrosis, the subtypes of papillary microcarcinoma, and the established prognostic factors.
METHODS: A total of 75 patients diagnosed with papillary microcarcinoma of the thyroid from January 2011 to December 2020 have been evaluated retrospectively, using demographic features, tumor size, subtype of the tumor, surgical margin status, unifocality, lymphovascular invasion, extracapsular spread and lymph node metastasis as parameters. Hematoxylin and eosin slides were reviewed for interstitial fibrosis.
RESULTS: The study includes 13 males and 62 females, in a total of 75 patients. There were 51 patients (68%) with interstitial fibrosis and 24 (32%) patients without interstitial fibrosis. Among them, 45 (60%) were classic, 27 (36%) were follicular variant and 3 (4%) were other subtypes. Interstitial fibrosis is significantly associated with bilaterality (p = 0.023), multifocality (p = 0.004), capsule invasion (p < 0.001) and lymph node metastasis (p = 0.043). Evaluation of tumor sub groups showed significant increased risk of lymphovascular invasion in the follicular variant (p = 0.019).
CONCLUSIONS: Although the relationship of interstitial fibrosis and prognosis of other cancer types has been discussed, there are few studies in the literature regarding its effect on the prognosis of papillary microcarcinoma. Our results show that interstitial fibrosis can be used as a risk factor. However, new studies are needed to clearly reveal the physiopathology of interstitial fibrosis and its effect on tumorigenesis.

Silicosis due to artificial stone (AS) has emerged over the last decade as an increasing global issue. We report the first eight UK cases. All were men; median age was 34 years (range 27-56) and median stone dust exposure was 12.5 years (range 4-40) but in 4 cases was 4-8 years. One is deceased; two were referred for lung transplant assessment. All cases were dry cutting and polishing AS worktops with inadequate safety measures. Clinical features of silicosis can closely mimic sarcoidosis. UK cases are likely to increase, with urgent action needed to identify cases and enforce regulations.

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Fibrosis is a marker of chronic kidney disease (CKD) and consists of the accumulation of the extracellular matrix (ECM) components, causing the progressive deterioration of kidney function. Human liver stem cells (HLSCs) have anti-fibrotic activity, and HLSC-derived extracellular vesicles (EVs) mediate this effect. Herein, we evaluated the ability of HLSC-EVs to reverse renal and cardiac alterations in a murine model of partial nephrectomy (PNx) that mimics human CKD development. Furthermore, we investigated the contribution of extracellular matrix remodeling-related proteases to the anti-fibrotic effect of HLSC-EVs. PNx was performed by ligation of both poles of the left kidney, followed one week later by the removal of the right kidney. EV treatment started 4 weeks after the nephrectomy, when renal and cardiac alternations were already established, and mice were sacrificed at week eight. HLSC-EV treatment improved renal function and morphology, significantly decreasing interstitial fibrosis, glomerular sclerosis, and capillary rarefaction. This improvement was confirmed by the decreased expression of pro-fibrotic genes. Moreover, EV treatment improved cardiac function and reduced cardiac fibrosis. HLSC-EVs shuttled different proteases with ECM remodeling activity, and matrix metalloproteinase 1 (MMP-1) was involved in their anti-fibrotic effect on renal tissue. HLSC-EV treatment interferes with CKD development and ameliorates cardiomyopathy in PNx mice.

BACKGROUND: Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline.
OBJECTIVE: Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question.
RESULTS: In our study, CD206+ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99mTc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99mTc-tilmanocept was able to accurately detect and quantify the increase in CD206+ macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206+ lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206+ macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy.
CONCLUSIONS: These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF.

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