Unknown Etiology Research Articles

Research on the Influence of Air Pollutants and Meteorological Factors on Kawasaki Disease

PurposeKawasaki disease (KD), an acute systemic vasculitis of unknown etiology, has attracted widespread attention regarding the triggering role of environmental factors in its development. We assessed the effects of air pollutants and meteorological factors on KD, providing evidence for the etiology of KD and data guidance in Northwest China.MethodsThis time-stratified case-crossover study combined KD inpatient data with air pollutant and meteorological data. We completed individual exposure assessment using ArcGIS 10.8.1 according to the patient’s home address. The associations between air pollutants, meteorological factors, and KD on the previous 0–2 days before disease onset were evaluated through conditional logistic regression.ResultsWe found that each 10 μg m−3 increment of air PM10 at 1-day delay causes a 1.6% increase in the risk of KD (95% CI: 1.001–1.031). PM2.5 was associated with the risk of KD in males at 1-day delay (OR: 1.074, 95% CI: 1.003–1.149). SO2 exposure during the warm season was significantly associated with the risk of KD in children (OR: 1.144, 95% CI: 1.004–1.304). Temperature exposure is associated with the risk of KD, with the maximum effect occurring on the day of onset (OR: 1.060, 95% CI: 1.021–1.101).ConclusionExposure to particulate matter can increase the risk of KD in children, sex, age and season may modify the effects of particulate matter on KD. In addition, exposure to SO2 during the warm season had a stronger response to KD, and females and patients aged 2–3 and 5 years and above were more sensitive to SO2. Temperature exposure in meteorological factors can significantly increase the risk of KD, with males and patients aged 1–2 years being susceptible group.Graphical

Neutralizing Antibodies against California Serogroup Orthobunyaviruses in Human Serum Samples, Montana, USA.

Viral encephalitis is often underreported and undiagnosed. To understand the potential causes of viral encephalitis in the state of Montana, USA, we examined the relative incidence of human infections for the California serogroup (CSG) of Orthobunyaviruses by screening random convenience serum samples obtained from different hospitals across Montana. We initially screened deidentified samples for neutralizing antibodies against Jamestown Canyon virus (JCV), a CSG virus that has caused encephalitis in Montana. We then analyzed JCV-positive samples for neutralization of other CSG viruses, and detected neutralizing antibodies against La Crosse virus, California encephalitis virus, and Trivittatus virus. We also found a high level of cross-reactivity, particularly between JCV and California encephalitis virus. Our findings indicate that the relative CSG virus infection rates in humans are quite high, between 21% and 40%. Clinicians should consider CSG viruses in differential diagnosis for cases of encephalitis of unknown etiology in Montana.

Periodontic-orthodontic-orthognathic combined treatment of adult Class Ⅱ skeletal malocclusion with idiopathic gingival fibromatosis: a case report

Idiopathic gingival fibromatosis is a rare, benign condition of unknown etiology characterized by extensive gingival overgrowth. This case reports a severe skeletal Class Ⅱ adult female patient with idiopathic gingival fibromatosis. The patient underwent multidisciplinary treatment involving periodontics, orthodontics, and orthognathic surgery, resulting in remarkable crown height elongation, substantial improvements in occlusal function and aesthetics, and stable long-term follow-up outcomes. This case provides a reference for future clinical practice.

Hesperidin alleviates endothelial cell inflammation and apoptosis of Kawasaki disease through inhibiting the TLR4/IĸBα/NF-ĸB pathway.

Hesperidin alleviates endothelial cell inflammation and apoptosis of Kawasaki disease through inhibiting the TLR4/IĸBα/NF-ĸB pathway.

Oxalate nephropathy analysis: A case series from a single center.

Enteric hyperoxaluria is a common cause of secondary oxalate nephropathy (ON), and pancreatic exocrine insufficiency (PEI) is one of the causes of enteric hyperoxaluria. Due to atypical clinical symptoms or elusive etiology, the incidence of PEI is often underestimated. For patients with ON, it is crucial to screen for PEI and its etiology. Cases with pathological diagnosis of ON and acute kidney injury (AKI) during January 2023 to December 2023 were retrospectively enrolled. The datasets of clinical manifestation, kidney pathology, treatment, and prognosis were collected. Fecal elastase-1 was employed to test pancreatic exocrine function. Genetic testing, bioinformatics analyses, and minigene splicing assay were performed on patients diagnosed with chronic pancreatitis (CP). Among 6 patients diagnosed with ON, 2 patients had increased intake of oxalate/oxalate precursors, 2 patients had increased intestinal oxalate absorption due to PEI, one patient both had increased intake and absorption, with one case being of unknown etiology. . Among the 3 patients with PEI, 2 were diagnosed with CP and genetic testing further discovered mutations in SPINK1 or PRSS1 . Renal function was completely recovered in 2 patients, progressed to end-stage kidney disease in 1, and the remaining patients showed varying degrees of kidney function recovery. A kidney biopsy can help physicians determine the cause of AKI. Once diagnosed with secondary ON, screening for PEI is recommended, especially when considering enteric hyperoxaluria as the cause. The etiology of PEI should be investigated. Genetic testing is advised for CP patients without clear etiology or recurrent acute pancreatitis.

Clinical implications of idiopathic pulmonary fibrosis and lung cancer

Idiopathic pulmonary fibrosis (IPF) is characterized by chronic progressive fibrosis of the lungs of unknown etiology. The prognosis of IPF is poor, with a median survival of 3 to 5 years. Lung cancer is one of the most frequently associated comorbidities of IPF, often resulting in grave outcomes. Patients with IPF have a higher risk for lung cancer than the general population. Lung cancer frequently develops in older male IPF patients with smoking history. Squamous cell carcinoma is the most common histological type, followed by adenocarcinoma. Such cancers typically develop abutting or within fibrosis. One of the major obstacles in making therapeutic decisions for these patients is the complications after treatment and subsequent poor prognosis. Numerous studies have reported post-treatment complications, such as acute exacerbation of IPF, pneumonia, and persistent air leakage, and their impact on survival. Higher mortality rates have consistently been reported among patients diagnosed with both IPF and lung cancer compared to those with either IPF or lung cancer alone. Thorough risk assessment for complications, selection of appropriate therapeutic modality, and use of antifibrotic agents, such as pirfenidone or nintedanib, may help prevent complications and improve survival. Nevertheless, further research is necessary to establish optimal treatment strategies for patients diagnosed with IPF and lung cancer.

Adoptive Transfer of T Cells as a Potential Therapeutic Approach in the Bleomycin-Injured Mouse Lung.

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an unknown etiology and complex pathophysiology that are not fully understood. The disease involves intricate cellular interplay, particularly among various immune cells. Currently, there is no treatment capable of reversing the fibrotic process or aiding lung regeneration. Hepatocyte growth factor (HGF) has demonstrated antifibrotic properties, whereas the adoptive transfer of modified T cells is a well-established treatment for various malignancies. We aimed to understand the dynamics of T cells in the progression of lung fibrosis and to study the therapeutic benefit of adoptive T cell transfer in a bleomycin-injured mouse lung (BLM) model. T cells were isolated from the spleen of naïve mice and transfected invitro with mouse HGF plasmid and were administered intratracheally to the mice lungs 7 days post-bleomycin injury to the lung. Lung tissue and bronchoalveolar lavage were collected and analyzed using flow cytometry, histology, qRT-PCR, ELISA, and hydroxyproline assay. Our findings demonstrate the successful T cell therapy of bleomycin-induced lung injury through the adoptive transfer of HGF-transfected T cells in mice. This treatment resulted in decreased collagen deposition and a balancing of immune cell exhaustion and cytokine homeostasis compared with untreated controls. Invitro testing showed enhanced apoptosis in myofibroblasts induced by HGF-overexpressing T cells. Taken together, our data highlight the great potential of adoptive T cell transfer as an emerging therapy to counteract lung fibrosis.

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome: An Update

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an autoinflammatory disorder of unknown genetic etiology typically characterized by recurrent fever episodes, pharyngitis, aphthous stomatitis and cervical lymphadenitis. The syndrome runs a benign course with fever episodes recurring in regular intervals and usually resolves around adolescence, even though, for a subset of patients, it persists through adulthood. It is considered a condition of multifactorial etiology, a syndrome that is triggered by environmental factors in genetically predisposed individuals. Increasing evidence points towards a correlation between monogenic autoinflammatory syndromes and PFAPA syndrome both in pathogenesis and therapeutic approaches. In this review, we present an update of the current literature on PFAPA and focus on new data on genetics of PFAPA and the association of PFAPA with other autoinflammatory diseases.

Fibrotic Pulmonary Sarcoidosis-From Pathogenesis to Management.

Sarcoidosis is a multiorgan, granulomatous disease of an unknown etiology. The characteristic feature of the disease is the formation of noncaseating granulomas. Spontaneous resolution occurs in most patients, but the clinical course may be chronic or progressive, complicated by pulmonary fibrosis, which is a major cause of mortality in sarcoidosis. Recent studies have provided new information on the immunological mechanisms of pulmonary fibrosis. Its pathogenesis includes the alteration of lymphocyte activity and the imbalance between their subpopulations, the polarization of macrophages to the profibrotic phenotype, and an imbalance between the activity of metalloproteinases and their tissue inhibitors. A multidisciplinary approach is required for the optimal management of fibrotic pulmonary sarcoidosis. Clinical symptoms, serum biomarkers, imaging, pulmonary function test results, other organ involvement, comorbidities, and complications should be considered when assessing disease activity and selecting the most appropriate treatment. The use of anti-inflammatory drugs is often discussed. There has been no consensus reached on whether antifibrotic agents should be added or used in monotherapy as initial treatment in such cases. This article will review all the information on fibrotic pulmonary sarcoidosis and present factors associated with fibrosis development, prognosis, and treatment options.

Deciphering the interplay: circulating cell-free DNA, signaling pathways, and disease progression in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lung disease with an unknown etiology and a short survival rate. There is no accurate method of early diagnosis, and it involves computed tomography (CT) or lung biopsy. Since diagnostic methods are not accurate due to their similarity to other lung pathologies, discovering new biomarkers is a key issue for diagnosticians. Currently, the use of ccf-DNA (circulating cell-free deoxyribonucleic acid) is an important focus due to its association with IPF-induced alterations in metabolic pathways, such as amino acid metabolism, energy metabolism, and lipid metabolism pathways. Other biomarkers associated with metabolic changes have been found, and they are related to changes in type II/type I alveolar epithelial cells (AECs I/II), changes in extracellular matrix (ECM), and inflammatory processes. Currently, IPF pathogenetic treatment remains unknown, and the mortality rates are increasing, and the patients are diagnosed at a late stage. Signaling pathways and metabolic dysfunction have a significant role in the disease occurrence, particularly the transforming growth factor-β (TGF-β) signaling pathway, which plays an essential role. TGF-β, Wnt, Hedgehog (Hh), and integrin signaling are the main drivers of fibrosis. These pathways activate the transformation of fibroblasts into myofibroblasts, extracellular matrix (ECM) deposition, and tissue remodeling fibrosis. Therapy targeting diverse signaling pathways to slow disease progression is crucial inthe treatment of IPF. Two antifibrotic medications, including pirfenidone and nintedanib, are Food and Drug Administration (FDA)-approved for treatment. ccf-DNA could become a new biomarker for IPF diagnosis to detect the disease at the early stage, while FDA-approved therapies could help to prevent late conditions from forming and decrease mortality rates.

Use of Biologic Therapy in AA Amyloidosis Patients Undergoing Dialysis-A Systematic Literature Review.

The advent of biological agents has provided significant therapeutic opportunities for patients with AA amyloidosis. However, when these patients reach end-stage renal disease and begin dialysis, some clinicians may discontinue biological treatments due to the heightened risk of infections. Given that AA amyloidosis is a progressive condition, there is a potential for the disease to affect additional organs in these patients. Consequently, we aimed to evaluate the benefits and risks associated with biological agents in AA amyloidosis patients receiving dialysis. We performed a systematic literature review in Cochrane Database and MEDLINE about the use of biologic agents in AA amyloidosis patients undergoing dialysis. We identified fifty-five patients across twenty-two studies. Familial Mediterranean fever was the etiology in 21 patients (71.4% anakinra and 28.6% canakinumab), rheumatoid arthritis in 17 patients (52.9% etanercept and 47.1% tocilizumab), unknown etiology in 8 patients (62.5% anakinra and 37.5% tocilizumab), ankylosing spondylitis in 5 patients (40% etanercept, 40% adalimumab, and 20% infliximab), hidradenitis suppurativa in 3 patients and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in 1 patient. Biologic agents were effective or partially effective for primary disease control in 52 patients (94.5%). Two patients were able to discontinue dialysis. Most frequent side effects were infections (8 episodes in 7 patients). Eight patients died (5 due to infections, one due to cardiac causes and two due to pulmonary hemorrhage). Biologic agents are effective in AA amyloidosis patients that are treated with dialysis and seem to have an acceptable safety profile.

Pancreatic sarcoidosis: A case report and literature review.

Sarcoidosis is a multisystem disease of unknown etiology that usually involves the lungs and hilar lymph nodes and rarely involves the digestive system other than the liver. A woman with no medical history presented with 2 pulmonary nodules and a pancreatic mass on chest computed tomography (CT) because of sputum production and shortness of breath. Ultrasound bronchoscopy and pathology showed pulmonary sarcoidosis. Oral prednisone acetate. In the following year of follow-up, the pancreatic, lung and mediastinal lesions were significantly reduced. Corticosteroid therapy may therefore constitute a different kind of diagnosis.

Decreased Lactococcus lactis and propionic acid in feces of patients with Moyamoya disease: Possible implications of immune dysregulation.

Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive steno-occlusive lesions in the terminal portion of the internal carotid artery. Despite its unknown etiology, immune dysregulation is regarded as a critical trigger for delineating the pathophysiology of MMD. The gut microbiota produces short-chain fatty (SCFA) and organic acids, influencing immune regulation and vascular remodeling. We aimed to characterize the gut microbiota in patients with MMD. Sixteen patients with MMD and sixteen healthy controls were included in this study. We performed 16S rRNA sequencing of fecal samples and analyzed microbiome diversity and composition, and quantified SCFA and organic acid levels using liquid chromatography. There were no significant differences in α- and b-diversities among feces from the MMD patients and controls. However, 16S rRNA sequencing identified defective Lactococcus lactis (0 ± 0 in the MMD patients vs. 0.026 ± 0.084 in healthy controls, p = 0.0181) and abundant Gordinobacter pamelaeae (0.030±0.039 in the patients vs. 0.001±0.005 in healthy controls, p = 0.003) are strongly linked to MMD. Propionic acid levels were significantly lower in feces of the MMD patients compared to healthy controls (0.83 ± 0.34 mg/g in the MMD patients vs. 1.20 ± 0.55 mg/g in healthy controls, p = 0.028). Decreased Lactococcus lactis can result in reduced lactic acid and propionic acid levels in the feces of the patients. This imbalance in the gut microbiome and SCFA/organic acid levels could contribute to immune dysregulation underlying the vascular remodeling seen in MMD.

A review of the link between psychological stress and inflammatory bowel disease exacerbation

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting illness characterized by episodes of inflammation in the gastrointestinal tract. This condition affects several million people worldwide and has become more prevalent in recent decades. It frequently manifests in individuals aged 15–35 and is observed among high school-aged adolescents and college-aged adults. Despite extensive research, the root cause of IBD remains unknown. The largely unknown etiology of the illness, variability of symptoms, and the need for improvement in the efficacy of IBD treatment underscore the significance of psychosocial factors on the influence of the condition. This review examines three lines of stress research—stressful life events, daily stress, and perceived stress—to evaluate the association between psychological stress and IBD exacerbation. A review of empirical evidence shows a robust link between psychological stress and disease activity in IBD, suggesting that psychological stress is a risk factor for disease exacerbation. Four major limitations involving psychological stress in the IBD literature are identified: (1) the influence of daily stress on IBD exacerbation, (2) stress conceptualization and the operationalization of disease activity, (3) directionality between stress and IBD activity, and (4) moderators of the link between stress and disease exacerbation. Future directions for stress research in IBD are proposed.

Efficacy of Radiotherapy in Patients with Relapsing Primary Rosai–Dorfman Disease of the Nasal Cavity

Rosai–Dorfman disease (RDD) is a rare proliferative disorder characterized by an overproduction of a type of immune cell called histiocytes, with unknown etiology. Although extranodal involvement is not uncommon, it is rarely seen within the nose. The available data are limited, and currently, there are no established guidelines for managing RDD. Different therapeutic options have been described, including corticosteroids, surgery, radiotherapy, or chemotherapy. This study aims to evaluate the potential benefit of radiotherapy in patients with nasal Rosai–Dorfman disease to improve the current diagnostic and therapeutic management. Herein, we report the case of a 54-year-old female patient with nasal RDD refractory to systemic corticosteroid therapy and transnasal endoscopic resection. She received fractionated low-dose radiotherapy with a total dose of 30 cGy administered in 2 cGy daily fractions. Complete remission was achieved, highlighting the potential role of radiotherapy as an effective therapeutic option for relapsing or steroid-refractory cases. This is one of the few well-documented cases reported with nasal Rosai–Dorfman disease treated with radiotherapy. Ongoing research on novel therapies offers hope for improved outcomes in relapsing cases that fail to respond to conventional treatments.

Clinical indices and laboratory markers for evaluating the immune-mediated inflammation in rheumatoid arthritis: the impact of COVID-19

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown etiology that represents a considerable burden for both the patient and the healthcare system. The degree to which inflammation is being controlled determines the prognosis; therefore, achieving remission or low disease activity is of paramount importance to medical practitioners. The effectiveness of the currently employed treatment regimen for a specific patient is determined by the disease activity indices and the change in their values during treatment. The commonly used RA disease activity indices are the result of a painstaking search for the optimal set of clinical, laboratory and instrumental parameters reflecting the underlying pathogenesis of inflammation in RA spanning half a century. Routine laboratory tests not included in these indices can nevertheless provide additional valuable information regarding the disease. The new coronavirus infection, COVID-19, has similar pathogenetic mechanisms with immunoinflammatory rheumatic diseases, and its clinical and laboratory consequences in the form of postcovid-19 syndrome, make it difficult to assess the activity of RA using existing activity indices, raise the question of the need to take them into account when assessing the effectiveness and choosing the tactics of treatment of a patient with RA.

Effect of a new type of Healthy and live Food Supplement on Osteoporosis Blood Parameters and Induced Rheumatoid Arthritis in Wistar Rats

Summary: Osteoporosis is a skeletal disorder, characterized by a decrease in bone strength and puts the individual at risk for fracture. On the other hand, rheumatoid arthritis is a systemic disease of unknown etiology that causes inflammation of the joints of the organs. Purpose: Due to the destructive effects of these diseases and its increasing prevalence and lack of appropriate medication for treatment, the present study aimed to evaluate the therapeutic effect of a new type of healthy and live food supplement on rheumatoid arthritis and induced osteoporosis in rats. Methods: In this research, healthy and live food powder were synthesized by a new and green route. This organic biomaterial was named NBS. The NBS food supplement had various vitamins, macro and micro molecules, and ingredients. The new healthy and nutritious diet showed that the use of this supplement led to the return of the parameters to normal levels. Results: The concentration of 12.5 mg/ kg showed the least therapeutic effect and 50 mg/ kg had the highest therapeutic effect for osteoporosis. The results of blood parameters involved in inflammation in both healthy and patient groups showed that the use of complete adjuvant induction causes joint inflammation. In the study of the interaction of the concentrations, it was observed that the concentration of 50 mg/ kg had the highest therapeutic effect against the disease in the studied mice. Conclusion: The results showed that the new healthy and viable supplement restores the blood osteoporotic and rheumatoid factors of the mice to normal.

Rhoifolin improves bleomycin-induced fibrosis in vivo and cell damage in vitro both related to NRF2/HO-1 pathway

BackgroundPulmonary fibrosis (PF) is a chronic interstitial lung illness characterized by its high worldwide prevalence, unknown etiology, and dismal prognosis. Lonicerae Japonicae Flos, a commonly used traditional Chinese medicine for treating PF, is rich in Rhoifolin (ROF). Although numerous studies have demonstrated the anti-inflammatory properties of ROF, its potential anti-fibrotic effects remain uncertain.MethodsIn this study, we established a PF model in Sprague-Dawley (SD) rats utilizing Bleomycin (BLM). We then assessed the impact of ROF on lung histology and appearance, measured the content level of Superoxide dismutase (SOD) in rat serum, and analyzed changes in α-SMA, TGF-β relative mRNA expression using PCR, measured SMAD Family Member 7 (Smad7), and Heme Oxygenase-1 (HO-1) protein expression in rat lung tissue by Western Blot. Additionally, we induced a cell injury model in A549 cells with BLM. Then after ROF administration, we detected the cell viability by MTT assay, measured N-cadherin, α-SMA, and Vimentin mRNA levels via real-time PCR, and analyzed the expression changes of N-cadherin, Nuclear factor erythroid 2-related factor 2(Nrf2), HO-1, Smad7 proteins by Western Blot.ResultsThe results indicated that ROF mitigated lung tissue damage and reduced the degree of PF in the lung tissue of rats with PF. Furthermore, In vivo, ROF reduced the expression of N-cadherin protein while increasing the expression of Smad7, and HO-1 proteins and decreasing the relative mRNA expression of α-SMA and TGF-β, and increased the expresson of SOD in rat serum In vitro, cell injury was induced in A549 cells using BLM. After ROF administration, the relative mRNA expression of α-SMA, N-cadherin, and Vimentin decreased significantly, and the protein expression of N-cadherin decreased, while the protein expression of Nrf2, HO-1, and Smad7 increased significantly.ConclusionThis study demonstrates that ROF can mitigate the symptoms of PF to a certain degree, and its mechanism of action is intimately linked to the Nrf2/HO-1 signaling pathway. Therefore, this study indicates that ROF may serve as a potential therapeutic agent for treating PF.Clinical trial numberNot applicable.

Genetic and protein structure prediction analyses identify a rare pathogenic PKD1 variant causing autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic kidney disorders. The diagnosis of ADPKD requires imaging findings showing multiple kidney cysts or genetic testing, in cases where a family history is unknown. We report a patient diagnosed with ADPKD based on the identification of a rare PKD1 variant. The patient was a 41-year-old female in whom cysts and calcification in the kidneys were incidentally detected. Whole-exome sequencing identified a rare PKD1 variant (NM_001009944.3: c.11557G > A/p.E3853K). Protein structure prediction of the PKD1-PKD2 complex showed that the variant may be pathogenic, leading to the diagnosis of autosomal dominant polycystic kidney disease. A detailed family history revealed that her relatives also had ADPKD, further supporting the diagnosis of ADPKD. Comprehensive genetic analysis and protein structure prediction led to the diagnosis of ADPKD and the identification of rare causative genes. These methods are useful for diagnosing hereditary kidney diseases of unknown etiologies.

The Impact of Comorbidities on the Discontinuation of Antifibrotic Therapy in Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown aetiology. Evidence on the progression of idiopathic pulmonary fibrosis (IPF) following the introduction of antifibrotic therapies still indicates a generally poor prognosis. IPF is associated with both respiratory and non-respiratory comorbidities, which can worsen symptoms and impact overall survival. Background/Objectives: The study aimed to investigate the effect of these comorbidities on the early and permanent discontinuation of pirfenidone or nintedanib in IPF patients. Methods: In this single-centre retrospective study, 101 patients diagnosed with IPF according to ATS/ERS/JRS/ALAT guidelines were treated with AFT. Clinical data were collected at 12 months prior to and up to 24 months following treatment initiation, including age, gender, smoking history, and the presence of respiratory and non-respiratory comorbidities. Results: The data showed that 21 patients (20.8%) discontinued treatment within the first 12 months. Additionally, pre-treatment comorbidities were not statistically correlated with the suspension of antifibrotic treatment. Among the overall cohort, 77 patients (76.2%) had at least one comorbidity and 27 (26.7%) had three or more comorbidities. Notably, 24 (23.8%) had respiratory comorbidities, while 75 (74.3%) had non-respiratory comorbidities. Conclusions: This real-life study emphasises the complexities involved in managing IPF, particularly regarding adherence to treatment when significant comorbidities are present. The evidence suggests that in patients with IPF, pre-treatment respiratory or non-respiratory conditions do not affect AFT discontinuation.