Search Results (27)

Background: Interstitial lung disease (ILD) is characterized by pulmonary inflammation and fibrosis associated with persistent and refractory cough that significantly hinders quality of life. Conventional treatments for ILD-associated cough have shown limited efficacy, necessitating alternative therapeutic approaches. Gefapixant, a P2X3 receptor antagonist, can potentially alleviate chronic cough by inhibiting the ATP-mediated activation of sensory C-fibers, but its efficacy in ILD-associated cough remains unclear. This study observed the effects of gefapixant on ILD-associated refractory chronic cough. Methods: This prospective study enrolled patients with ILD-associated refractory chronic cough who received gefapixant at Sapporo Medical University Hospital between July 2022 and November 2023. Cough frequency, Leicester Cough Questionnaire (LCQ) score, cough severity visual analog scale (Cough VAS), and taste VAS were evaluated at baseline and at 2, 4, and 8 weeks after gefapixant administration. Results: Six patients completed the study. Their ILD subtypes included idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated ILDs (CTD-ILDs). After 8 weeks, the cough frequency decreased from 88.5 to 44.3 episodes per 30 min, LCQ scores increased from 8.3 to 13.6, and cough VAS scores decreased from 75.8 to 40.2. However, statistical significance was not reached due to high interindividual variability, with gefapixant being effective in some and ineffective in others. The most common adverse event was taste disorder, leading to discontinuation in one patient, but symptoms tended to lessen over the course of treatment. Conclusions: Gefapixant appears to be effective in reducing refractory cough related to ILD, although these results were not statistically significant because its effectivity widely varied across individuals. Further investigation is needed to identify patient subgroups with the greatest potential for treatment responsiveness. Full article

Background/Objectives: The usefulness of presepsin, which is released from macrophages, in acute exacerbation of interstitial lung diseases (AE-ILDs) is unknown. We aimed to investigate the utility of monitoring presepsin with other AE-ILD markers before and after steroid pulse therapy in AE-ILDs. Methods: This pilot single-center retrospective observational study involved 16 patients with AE-ILDs, including the AE of idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia and rapidly progressive connective tissue disease-associated ILD. Patients who survived 90 days were assigned to the survival group (n = 9). The remaining patients were classified in the non-survivor group (n = 7). To evaluate the therapeutic efficacy of steroid pulse therapy, specific serum markers were selected—presepsin, as a novel AE-ILD marker, and surfactant protein D, C-reactive protein, and lactate dehydrogenase (LDH), as classical AE-ILD markers. Results: Thirteen out of sixteen patients with AE-ILDs showed high presepsin levels (presepsin ≥ 470 pg/mL) before steroid pulse therapy. The post-/pre-presepsin ratio and the post-/pre-LDH ratio, calculated by dividing the presepsin and LDH levels after therapy by the levels before therapy, respectively, showed a positive correlation (r = 0.579, p = 0.021). As a result of this correlation, the post-/pre-presepsin–LDH index was created, obtained from the “post-/pre-presepsin ratio” multiplied by the “post-/pre-LDH ratio”. In a receiver operating characteristic curve analysis for non-survival, the post-/pre-presepsin–LDH index showed good discrimination as a prognostic marker for a poor outcome (AUC: 0.873, 95% confidence interval: 0.655–0.999). Conclusions: Tracking presepsin and LDH simultaneously may be useful for determining treatment response to steroid pulse therapy in the clinical management of AE-ILDs. Full article

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Methods: This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases “Lazzaro Spallanzani” in Rome, Italy, over three years (2019–2022). Results and Conclusions: Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions. Full article

Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy (NVC) changes and increased morbidity and mortality rates. Early diagnosis is crucial in order to prevent the progression of ILD, prevent respiratory failure and enhance the patient’s overall quality of life. The most common paraclinical investigations are high-resolution computed tomography (HRCT) and functional respiratory tests such as forced vital capacity (FVC) and the diffusing capacity of the lungs for carbon monoxide (DLCO). The most frequent CTD associated with both ILD and NVC changes is systemic sclerosis. The “late” scleroderma pattern was the most common abnormality identified in NVC results in SSc patients. Other autoimmune diseases were also correlated with ILD and NVC changes, especially when the Raynaud phenomenon was present. Low capillary density was associated with the presence and severity of ILD and a reduction in FVC and DLCO. NVC can also differentiate the capillaroscopic changes in some particular types of ILD, such as the usual interstitial pneumonia (UIP) pattern from the non-specific interstitial pneumonia (NSIP) pattern. Nevertheless, further extensive research is necessary in order to establish the diagnostic value of NVC in CTD-ILD in clinical practice. Full article

This study evaluates the usefulness of serum KL-6, SP-D and TGF-β1 levels in assessing lung impairment and predicting interstitial lung disease (ILD) short-term progression in patients with interstitial pneumonia with autoimmune features (IPAF). A total of 24 patients with IPAF, 21 with connective tissue disease-associated ILD (CTD-ILD) and 23 with CTD without ILD were followed for 1 year. Serum levels of KL-6, SP-D and TGF-β1 were measured and their associations with disease severity and progression were analysed. KL-6, SP-D and TGF-β1 levels were significantly higher in IPAF and CTD-ILD patients compared to CTD without ILD (p < 0.0001, p = 0.0005 and p = 0.0001, respectively). KL-6 (r = 0.45, p = 0.002) and SP-D (r = 0.35, p = 0.02) levels correlated with lung involvement in HRCT in the ILD group. In IPAF, KL-6 levels correlated with pulmonary function tests (FVC%, TLCO%, and 6MWD) and SpO2, while SP-D correlated with 6MWD and SpO2. In CTD-ILD, KL-6 and SP-D levels were positively correlated with BAL cell count (KL-6: r = 0.58, p = 0.04; SP-D: r = 0.63, and p = 0.02). KL-6 also showed a negative correlation with the time since symptom onset (r = −0.51, p = 0.02). No significant associations were found between the baseline biomarker levels and ILD progression risk. KL-6 and SP-D may serve as potential biomarkers for assessing lung impairment in IPAF, though their predictive value for short-term prognosis remains uncertain. Full article

Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4⁺ T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD. Full article

Background: Antibodies against Ku have been described in patients with various connective tissue diseases. The objective of this study was to describe the clinical, functional, and imaging characteristics of interstitial lung disease in patients with anti-Ku antibodies. Methods: This single-center, retrospective observational study was conducted at a tertiary referral institution. Patients with positive anti-Ku antibodies and interstitial lung disease identified between 2007 and 2022 were included. Clinical, immunological, functional, and imaging data were systematically reviewed. Results: Nineteen patients (ten females) with a mean age of 59 ± 12.6 years were included. The most frequent associated diagnosis was systemic sclerosis (42%), followed by rheumatoid arthritis (26%), Sjögren syndrome, undifferentiated connective tissue disease, and overlap between systemic sclerosis and idiopathic inflammatory myopathy (scleromyositis). Imaging revealed frequent septal and intralobular reticulations and ground-glass opacities, with nonspecific interstitial pneumonia as the predominant pattern (53%). The mean forced vital capacity was 82% ± 26 of the predicted value, and the mean diffusing capacity for carbon monoxide was 55% ± 21. Over the first year of follow-up, the mean annual forced vital capacity decline was 140 mL/year (range: 0–1610 mL/year). The overall survival rate was 82% at 5 years and 67% at 10 years. Conclusions: Most patients with interstitial lung disease and anti-Ku antibodies presented with dyspnea, a mild-to-moderate restrictive ventilatory pattern, and reduced diffusing capacity for carbon monoxide. The CT pattern was heterogeneous but was consistent with nonspecific interstitial pneumonia in half of the patients. Full article

Background/Objectives: Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes. Methods: We conducted a retrospective review of hospitalized adult patients with AEs of ILDs from January 2019 to February 2024. Results: A total of 93 patients were enrolled: IPF (n = 42), iNSIP (n = 37), and CTD-ILDs (n = 14). The median age was 80 years (interquartile range: 74.0–86.0 years), with males comprising 64.5% (n = 60). AEs of ILDs predominantly occurred in winter and were particularly notable after summer 2023, coinciding with the lifting of COVID-19-related travel restrictions in Japan. Patient referrals from different areas (Northern Tama, East and/or Southern Tama, and other Tokyo metropolitan areas) were evenly distributed throughout the study period. Viral infections were detected in only two patients (SARS-CoV-2), and bacterial infections included methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The Cox regression analysis identified serum lactate dehydrogenase levels ≥350 IU/L and tachypnea (respiratory rate ≥ 30 breaths per min) on admission as prognostic factors for mortality, with a hazard ratio [HR] of 2.783 (95% confidence interval [CI]: 1.480–5.235, p = 0.001) and an HR of 3.332 (95% CI: 1.710–6.492, p < 0.001), respectively. Conclusions: AEs of ILDs predominantly occur in winter, and viral and bacterial infections are infrequently detected. Elevated serum LDH levels and tachypnea are crucial prognostic markers for mortality. This study highlights the seasonal trend in the AE of ILD and emphasizes the importance of specific prognostic indicators in clinical practice. Full article

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp’s, Kasukawa, Alarcón-Segovia, or Kahn’s diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91–201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00–1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients. Full article

Background and Objectives: Recently published articles reported an association between psoriasis and interstitial lung diseases (ILDs). The aim of this study is to evaluate the differences in ILD computed tomography (CT) patterns between smoker and never smoker plaque psoriasis (PP) patients under topical treatment without psoriatic arthritis (PA), inflammatory bowel disease (IBD) or connective tissue diseases (CTDs). Matherials and Methods: Two radiologists evaluated chest CT examinations of 65 patients (33 smokers, 32 never smokers) with PP. Results: Usual interstitial pneumonia (UIP) pattern was diagnosed in 36 patients, nonspecific interstitial pneumonia pattern in 19, hypersensitivity pneumonitis in 7 and pleuropulmonary fibroelastosis (PPFE) in 3 patients. UIP pattern showed a statistically significant higher frequency in smoker patients (p = 0.0351). Respiratory symptoms were reported in 80% of patients. Conclusions: ILDs seems to represent a new comorbidity associated with psoriasis. Moreover, a statistically significant association between smokers and UIP pattern in PP patients is found. Respiratory symptoms should be evaluated in PP patients, in collaboration with a radiologist and a pneumologist. However, further studies are required to better understand the epidemiology of ILDs in PP patients. Full article

Background: Frailty is a syndrome characterised by increased vulnerability to negative outcomes. Interstitial lung disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. Methods: We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including interstitial lung disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, systemic sclerosis-associated ILD, connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough contextually homogeneous studies were included, a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. Results: The review found three studies relating to frailty in asthma. No studies relating to pleural disease and frailty were identified. The median prevalence in asthma was 9.5% (IQR, 7.8–11.3). Six relevant studies incorporating 1471 ILD patients (age 68.3 ± SD2.38; 50% male) were identified, which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR, 25–50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31–4.15, I² 9%). One study reported a hospitalization rate of HR = 1.97(1.32–3.06) within 6 months in frail ILD patients. Conclusions: Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population. Full article

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area. Full article

Background: Interstitial lung diseases (ILDs) are a group of heterogeneous diseases characterized by inflammation and/or fibrosis of the lung interstitium, leading to a wide range of clinical manifestations and outcomes. Over the years, the literature has demonstrated the increased diagnostic accuracy and confidence associated with a multidisciplinary approach (MDA) in assessing diseases involving lung parenchyma. This approach was recently emphasized by the latest guidelines from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association for the diagnosis of ILDs. Methods: In this review, we will discuss the role, composition, and timing of multidisciplinary diagnosis (MDD) concerning idiopathic pulmonary fibrosis, connective tissue disease associated with ILDs, hypersensitive pneumonia, and idiopathic pneumonia with autoimmune features, based on the latest recommendations for their diagnosis. Results: The integration of clinical, radiological, histopathological, and, often, serological data is crucial in the early identification and management of ILDs, improving patient outcomes. Based on the recent endorsement of transbronchial cryo-biopsy in idiopathic pulmonary fibrosis guidelines, an MDA helps guide the choice of the sampling technique, obtaining the maximum diagnostic performance, and avoiding the execution of more invasive procedures such as a surgical lung biopsy. A multidisciplinary team should include pulmonologists, radiologists, pathologists, and, often, rheumatologists, being assembled regularly to achieve a consensus diagnosis and to review cases in light of new features. Conclusions: The literature highlighted that an MDA is essential to improve the accuracy and reliability of ILD diagnosis, allowing for the early optimization of therapy and reducing the need for invasive procedures. The multidisciplinary diagnosis of ILDs is an ongoing and dynamic process, often referred to as a “working diagnosis”, involving the progressive integration and re-evaluation of clinical, radiological, and histological features. Full article

Background and Objectives: The “interstitial pneumonia with autoimmune features” (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5–69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification. Full article

Objective: Current studies focus on the prevalence rate of lung cancer in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease (CTD-LID). Our aim was to investigate the prevalence of malignancies in patients with various subtypes of ILD. Methods: A total of 5350 patients diagnosed with ILD between January 2015 and December 2021 were retrospectively included. The prevalence of different malignancies and different ILDs was assessed using complete follow-up data. Results: A total of 248 patients (139 males; 65—IQR, 57 to 72—years) out of 5350 patients with ILD were confirmed with malignancies. A total of 69% of patients with ILD and malignances were older than 60 years old. The prevalence of malignancies in ILD patients was 4.6%, and lung cancer had the most common incidence of 1.9%, followed by malignancies in the digestive system of 0.9%. Among the different ILD subtypes, the prevalence of malignancies such as organizing pneumonia (OP), idiopathic pulmonary fibrosis (IPF), anti-neutrophil cytoplasmic antibodies-associated vasculitis-related ILD(AAV-ILD), nonspecific interstitial pneumonia (NSIP), CTD-ILD, hypersensitivity pneumonitis (HP), sarcoidosis, and other types of ILD was 6.8%, 5.0%, 4.7%, 4.3%, 2.5%, 2.2%, 1.2%, and 6.9%, respectively. The incidence of lung cancer as the most common tumor in IPF was 3.9%, with adenocarcinoma predominating (1.7%). The highest rate of malignancy occurring in RA of CTD-ILD was 2.4%. Conclusion: Older patients with ILD (≥60 years) including OP, IPF, AAV-ILD, NSIP, CTD-ILD, and HP, were associated with a higher incidence of malignancy, especially males aged from 60 to 69 years. These epidemiological results indicate that it is essential for physicians to pay more attention to the screening of and management strategies for different malignancies, according to the specific ILD subtypes. Full article