Risk Factors For Acute Exacerbation Research Articles

Identification of risk factors for acute exacerbation of idiopathic pulmonary fibrosis based on baseline high-resolution computed tomography: a prospective observational study

BackgroundThis study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT).MethodsThis prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed.ResultsA total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18–41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02–1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%.ConclusionsThis study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.

Risk factors of acute exacerbation and disease progression in young patients with COPD

ObjectiveWe aimed to elucidate the clinical factors associated with acute exacerbation and disease progression in young patients with chronic obstructive pulmonary disease (COPD).MethodsThis retrospective longitudinal observational study included patients with...

Radiofrequency Ablation in Patients with Interstitial Lung Disease and Lung Neoplasm: A Retrospective Multicenter Study

PurposeTo retrospectively investigate the safety and effectiveness of percutaneous radiofrequency (RF) ablation by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. Materials and MethodsPatients with lung neoplasm accompanied by ILD who underwent RF ablation between April 2002 and October 2017 at 7 institutions were investigated. Technical success rate and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. ResultsForty-nine patients with 64 lung neoplasms (mean diameter, 22.6 mm; range, 4–58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RF ablation. Acute exacerbations were seen in 5 sessions (8%, 7% with UIP pattern and 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8–30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥ 38°C after RF ablation were identified by univariate analysis (P = .0012 and P = .02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. ConclusionsRF ablation appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days after ablation and was associated with a 45% mortality rate.

Plasma sCD146 is a potential biomarker for acute exacerbation of chronic obstructive pulmonary disease.

This study examined the levels of soluble CD146 (sCD146) in plasma samples from patients with chronic obstructive pulmonary disease (COPD) and assessed the relationship between sCD146 and the severity of COPD. A total of 97 COPD patients were recruited from 20 medical centers in Jiangsu, China, including 13 stable subjects and 84 exacerbated subjects. The plasma sCD146 level in exacerbated subjects (28.77 ± 10.80 ng/mL) was significantly lower than that in stable subjects (38.84 ± 15.00 ng/mL). In the high sCD146 group, the proportion of subjects with modified Medical Research Council (mMRC) scores of 0-1 was higher, the proportion of subjects with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 was lower, and the proportion of subjects with ≥1 hospitalizations in the past year was lower. The plasma sCD146 level was negatively correlated with the COPD Assessment Test (CAT) score (r = -0.2664, p = 0.0087). Logistic regression analysis showed that sCD146 was an independent risk factor for acute exacerbation of COPD (AECOPD). Receiver operating characteristic (ROC) analysis suggested that sCD146 combined with sex, age, pulmonary function, and acute exacerbations in the past year had clinical value for the accurate identification of AECOPD, with an area under the ROC curve (AUC) of 0.908 (95% CI: 0.810-1.000, p < 0.001). In addition, there was a significant negative correlation between plasma sCD146 and S100A9 (r = -0.3939, p < 0.001).

Acute Exacerbation and Proposed Criteria for Progressive Pulmonary Fibrosis in Patients with Fibrotic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis

Background: Acute exacerbation (AE) occasionally develops in the course of fibrotic hypersensitivity pneumonitis (HP). Objective: The aim of the study was to compare AE of fibrotic HP with that of idiopathic pulmonary fibrosis (IPF). Methods: Consecutive patients with pathologically confirmed fibrotic HP and IPF diagnosed based on a multidisciplinary discussion were included in the analysis. AE in patients with fibrotic HP and IPF was evaluated retrospectively. Results: This study included 309 and 160 patients with fibrotic HP and IPF, respectively. Their 50% survival times were 96.1 and 78.0 months, respectively (hazard ratio [HR]: 0.54 [95% confidence interval, CI: 0.36–0.77], log-rank test; p < 0.001). Notably, the cumulative AE rates of fibrotic HP were 3% at 1 year and 10% at 3 years. Moreover, the corresponding rates of IPF were 8% at 1 year and 20% at 3 years (HR: 0.66 [95% CI: 0.45–0.93], log-rank test; p = 0.034). The 90-day survival rates from the AE onset of fibrotic HP and IPF were 75% and 64%, respectively (HR: 0.51 [95% CI: 0.31–0.83], log-rank test; p = 0.006). The respiratory function test on the physiological criteria of progressive pulmonary fibrosis (PPF) was a predictor of AE in fibrotic HP. However, the high-resolution CT (HRCT) changes in the criteria of PPF were not. Nevertheless, both the physiological and radiological criteria of PPF were a predictor of AE of IPF. Conclusion: AE of fibrotic HP has a lesser prognostic effect than that of IPF. HRCT criteria for PPF were not a risk factor for AE in patients with fibrotic HP.

The Impact of Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE).

Given the high risk of lung cancer (LC) in patients with combined pulmonary fibrosis and emphysema (CPFE), and the difficulty of early diagnosis, it is important to understand the impact of LC in these patients. The effect of LC on the development of acute exacerbation (AE) as a natural course of CPFE is still unknown. We retrospectively reviewed medical records of patients at the West China Hospital and enrolled 59 patients with CPFE combined with LC and 68 CPFE patients without LC for initial diagnosis matched in the same period. We compared the clinical characteristics and imaging features of CPFE patients with LC and without LC, and analyzed the associated factors for the prevalence of LC using binary logistic regression. Cox proportional hazards regression analysis was performed to explore risk factors of AE as a natural course of CPFE. Patients with CPFE combined with LC were more common among elderly male smokers. The most common pathological type of tumor was adenocarcinoma (24/59, 40.7%) and squamous cell carcinoma (18/59, 30.5%). Compared with those in the without LC group, the proportions of men, and ex- or current smokers, and the levels of smoking pack-years, serum CRP, IL-6, fibrinogen, complement C3 and C4 in patients with LC were significantly higher (p < 0.05). There was no significant difference in the proportion of natural-course-related AE (10.2% vs. 16.2%, p > 0.05) between the two groups. Logistic regression analysis demonstrated that pack-years ≥ 20 (OR: 3.672, 95% CI: 1.165-11.579), family history of cancer (OR: 8.353, 95% CI: 2.368-10.417), the level of fibrinogen > 4.81 g/L (OR: 3.628, 95% CI: 1.403-9.385) and serum C3 > 1.00 g/L (OR: 5.299, 95% CI: 1.727-16.263) were independently associated with LC in patients with CPFE. Compared to those without AE, CPFE patients with AE had significantly higher levels of PLR and serum CRP, with obviously lower DLCO and VC. The obviously increased PLR (HR: 3.731, 95% CI: 1.288-10.813), and decreased DLCO%pred (HR: 0.919, 95% CI: 0.863-0.979) and VC%pred (HR: 0.577, 95% CI: 0.137-0.918) rather than the presence of LC independently contributed to the development of natural-course-related AE in patients with CPFE. Pack-years, family history of cancer, the levels of fibrinogen and serum C3 were independently associated with LC in patients with CPFE. The presence of LC did not significantly increase the risk of AE as a natural course of CPFE. Clinicians should give high priority to CPFE patients, especially those with more severe fibrosis and systemic inflammation, in order to be alert for the occurrence of AE.

Nomogram for the acute exacerbation of acetylcholine receptor antibody-positive generalized myasthenia gravis.

An acute exacerbation of myasthenia gravis (MG) can lead to the life-threatening myasthenia crisis which can increase the in-hospital mortality. This study aimed to clarify the correlative factor of the severity and activity of MG and the predictors of its exacerbation. A prospective study was conducted to compare the clinical characteristics of acetylcholine receptor antibody (AChR-Ab)-positive generalized MG during acute exacerbation (AE) and in a stable state (SS). Logistic regression was used to determine risk factors, and a nomogram was developed. A total of 97 AChR-Ab MG patients were enrolled, of whom 44 had AE and 53 were in SS. The concentrations of AChR-Ab were 35.24 (23.26, 42.52) nmol/L and 19.51 (8.30, 36.93) nmol/L in the AE and SS groups (P = 0.005), respectively. The receiver operating characteristic curve showed that a single AChR-Ab predicted severity and acute exacerbation, with an area under the curve (AUC) of 0.679. Logistic regression analysis showed that, in addition to AChR-Ab (P = 0.018), bulbar symptoms (P = 0.001), interleukin (IL)-6 (P = 0.025), CD4+/CD8+ T cell ratio (P = 0.031), and CD19+ B cell proportion (P = 0.019) were independent risk factors for acute exacerbation of MG. The developed nomogram had an AUC of 0.878. The Hosmer and Lemeshow chi-square test was 4.37 (P = 0.929). AChR-Ab concentration was positively correlated with the severity and activity of MG. AChR-Ab concentration, alongside bulbar symptoms, IL-6 concentration, CD4+/CD8+ T cell ratio, and CD19+ B cell proportion can predict the acute exacerbation of MG.

Significance of Cardiometabolic Index in Predicting Acute Exacerbation of Stable Chronic Obstructive Pulmonary Disease for Clinical Nursing.

To evaluate the level of cardiometabolic index (CMI) to predict the risk of acute exacerbation in patients with stable chronic obstructive pulmonary disease (COPD), and to provide a basis for early identification and intervention of high-risk patients in clinical nursing work. Patients with stable chronic obstructive pulmonary disease who were admitted to the outpatient department of respiratory medicine in a tertiary hospital or followed up after discharge from January to December 2021 were retrospectively selected. CMI was measured and statistical analysis was performed to determine the optimal threshold for predicting acute exacerbation of chronic obstructive pulmonary disease. A total of 63 patients with chronic obstructive pulmonary disease were enrolled. The median number of episodes in the previous year was 1.00; 44 patients had ≥1 acute exacerbation. The CMI was positively correlated with the frequency of acute exacerbations and the British Medical Research Council (mMRC) score in the previous year, and negatively correlated with the percentage of forced expiratory volume in 1 second to the predicted value (FEV1% PRED). The cut-off point of CMI for predicting acute exacerbations in stable chronic obstructive pulmonary disease patients was 2.05, with a sensitivity of 0.864% and specificity of 0.842%. It is a risk factor for acute exacerbation in COPD patients. CMI can be used as a biological index to predict acute exacerbation in stable COPD patients. Clinical nursing needs to evaluate patients' CMI and provide personalized nursing intervention for patients with CMI≥2.05.

Clinical Deterioration and Lung Function Change in Patients With Concomitant Asthma and Bronchiectasis

Only limited data are available regarding the effects of bronchiectasis on the clinical course of asthma. This study evaluated longitudinal clinical outcomes according to bronchiectasis status in patients with asthma. This retrospective study included patients with asthma who underwent chest computed tomography and pulmonary function tests between January 2013 and December 2019. The annual incidence of episodes of moderate-to-severe acute clinical deterioration (exacerbations) and longitudinal changes in lung function were evaluated. Of 667 patients with asthma, 251 had bronchiectasis. Patients with bronchiectasis had significantly more history of tuberculosis and nontuberculous mycobacterial lung disease, and lower forced expiratory volume in 1 second and forced vital capacity, compared with patients without bronchiectasis, although there was no difference in smoking intensity and inhaled corticosteroid treatment. Bronchiectasis was significantly associated with higher annual rates of severe and moderate-to-severe acute exacerbations; it was also associated with greater risk of acute exacerbation during follow-up. The severity and progression of bronchiectasis were independent risk factors for acute exacerbation. There were no significant differences in annual decline of lung function according to bronchiectasis status or bronchiectasis progression. In patients with asthma, the presence and progression of bronchiectasis were significantly associated with increased risk of moderate-to-severe acute exacerbation, but they were not associated with longitudinal changes in lung function.

Clinical features of acute exacerbation in rheumatoid arthritis–associated interstitial lung disease: Comparison with idiopathic pulmonary fibrosis

BackgroundSeveral studies have reported that acute exacerbation (AE), which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD). However, the incidence, clinical features, and risk factors for AE, a major cause of death of RA-ILD patients, and the differences in clinical aspects of AE between RA-ILD and IPF have yet to be fully understood. MethodsWe retrospectively reviewed data on 149 RA-ILD patients and 305 IPF patients. We investigated the frequency of AE and compared the clinical data between RA-ILD with and without AE to clarify the risk factor for AE. We also compared the post-AE prognosis and cause of death between RA-ILD and IPF patients. ResultsTwenty-seven (18.1%) RA-ILD patients and 84 (27.5%) IPF patients developed AE. The median survival time (MST) after AE of RA-ILD and IPF was 277 days and 60 days, respectively (log rank, p = 0.038). In a multivariate analysis, hypoalbuminemia [odds ratio (O.R.) 0.090 (95%CI 0.011–0.733), p = 0.012] and % carbon monoxide diffusion capacity (%DLCO) [O.R. 0.810 (95%CI 0.814–0.964), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death of RA-ILD and IPF. ConclusionRA-ILD patients could develop AE, and AE was not uncommon in RA-ILD or IPF. %DLCO and hypoalbuminemia were predictive factors of AE in RA-ILD. The prognosis after AE of RA-ILD was significantly better than that of IPF. The most frequent cause of death in RA-ILD and IPF was AE.

Blood biomarkers associated with acute type II respiratory failure in COPD: A meta-analysis.

ObjectiveThis study aims to summarize the risk factors of type II respiratory failure in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to guide clinical treatment in time, and consequently reduce the serious impact of COPD on human health.MethodsFive databases were searched for relevant articles on risk factors of acute exacerbation of COPD combinate with type II respiratory failure. We calculated the standard mean difference (SMD), odds ratio (OR), and their 95% confidence interval (95% CI) utilizing a fixed‐effect model or a random‐effect model according to the level of heterogeneity.ResultsAs of 14 May 2021, 13 articles were included in our meta‐analysis. The results showed that low albumin and uric acid levels were the risk factors for type II respiratory failure in acute exacerbation of COPD patients, and the differences were statistically significant (albumin: SMD = −2.03, 95% CI: −2.81, −1.26; uric acid: SMD = −1.28, 95% CI: −1.41, −1.15). Besides, 10 other systematic markers have been reported to be the risk factors for type II respiratory failure of patients with acute exacerbation of COPD, but only in single study.ConclusionThe meta‐analysis results further confirm that low albumin and uric acid levels are risk factors for type II respiratory failure in acute exacerbation of COPD patients. Additionally, this analysis also summarizes many emerging inflammatory indicators, nutritional indicator, and cardiovascular system indicators to predict the progression of acute exacerbation of COPD to type II respiratory failure but only in single study.

Risk factors for acute exacerbation of interstitial lung disease following lung cancer resection: a systematic review and meta-analysis.

OBJECTIVESThe aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease (ILD) following lung cancer resection. METHODSWe performed a literature screening on the databases including PubMed, Embase, Ovid MEDLINE® and the Web of Science for related studies published up to January 2021. Eligible studies were included and data on risk factors related to postoperative AE were extracted. All analyses were performed with random-effect model.RESULTSA total of 12 studies of 2655 lung cancer patients with ILD were included in this article. The meta-analysis indicated that male [odds ratios (ORs) = 1.78, 95% confidence interval (CI): 1.02–3.11, P = 0.041], usually interstitial pneumonia pattern on CT (OR = 1.52, 95% CI: 1.06–2.17, P = 0.021), Krebs von den Lungen-6 [standardized mean difference (SMD) = 0.50, 95% CI: 0.06–0.94, P = 0.027], white blood cell (SMD = 0.53, 95% CI: 0.12–0.93, P = 0.010), lactate dehydrogenase (SMD = 0.47, 95% CI: 0.04–0.90, P = 0.032), partial pressure of oxygen (weighted mean difference = −3.09, 95% CI: −5.99 to −0.19, P = 0.037), surgery procedure (OR = 2.31, 95% CI: 1.42–3.77, P < 0.001) and operation time (weighted mean difference = 28.26, 95% CI: 1.13–55.39, P = 0.041) were risk factors for AE of ILD following lung cancer resection.CONCLUSIONSWe found that males, usually interstitial pneumonia pattern on CT, higher levels of Krebs von den Lungen-6, lactate dehydrogenase, white blood cell, lower partial pressure of oxygen, greater scope of operation and longer operation time were risk factors for AE of ILD following lung cancer resection. Patients with these risk factors should be more prudently selected for surgical treatment and be monitored more carefully after surgery.

Clinical Characteristics and Prognosis of Allergic Bronchopulmonary Aspergillosis: A Retrospective Cohort Study

BackgroundThe clinical features, treatment, and prognosis of allergic bronchopulmonary aspergillosis (ABPA) are not well-defined.ObjectiveWe aimed to investigate the clinical characteristics, therapy, and prognosis of ABPA to aid its clinical recognition.MethodsA total of 232 patients with ABPA were analyzed retrospectively. The characteristics of ABPA in terms of its misdiagnosis, computed tomography classification, therapy, and its relationship with asthma were analyzed, and risk factors for acute exacerbation of ABPA were analyzed based on follow-up data.ResultsOf the 232 ABPA patients, 132 had a history of misdiagnosis. Compared with the misdiagnosed patients, ABPA patients with central bronchiectasis, a high total eosinophil count, and mucus plugs were less likely to be misdiagnosed. Compared with serological ABPA, ABPA with central bronchiectasis was more likely to occur in older people and in patients with mucus plugs, and decreased forced vital capacity and diffusing capacity for carbon monoxide. ABPA patients with asthma were more likely to have bronchiectasis, decreased lung function in 1 s FEV1 and FEV1/FVC, and shorter time to first acute exacerbation compared with ABPA patients without asthma. Patients receiving glucocorticoids plus antifungal therapy had a longer time to first exacerbation than those receiving glucocorticoid therapy alone. Univariate and multivariate analyses revealed that duration of asthma history, duration of misdiagnosis, mucus plugs, and poor pulmonary function were risk factors for acute exacerbation of ABPA.ConclusionTo our knowledge, this is the largest sample size study of ABPA in China. ABPA patients with a history of asthma and/or central bronchiectasis on high-resolution computed tomography are prone to frequent acute exacerbations. The use of glucocorticoids combined with antifungal drugs can prolong the time to the first acute exacerbation in ABPA patients. Longer durations of asthma history and misdiagnosis, mucus plugs, and poor pulmonary function are risk factors for acute exacerbation of ABPA.

Asthma Patients Benefit More Than Chronic Obstructive Pulmonary Disease Patients in the Coronavirus Disease 2019 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) has raised many questions about the role of underlying chronic diseases on disease outcomes. However, there is limited information about the effects of COVID-19 on chronic airway diseases. Therefore, we conducted the present study to investigate the impact of COVID-19 on patients with asthma or chronic obstructive pulmonary disease (COPD) and ascertain risk factors for acute exacerbations (AEs).Methods: This single-center observational study was conducted at the Second Xiangya Hospital of Central South University, involving asthma or COPD patients who had been treated with inhaled combination corticosteroids (ICSs), such as budesonide, and one long-acting beta-2-agonist (LABA), such as formoterol, for at least a year before the COVID-19 pandemic. We conducted telephone interviews to collect demographic information and clinical data between January 1, 2019, and December 31, 2020, focusing on respiratory and systemic symptoms, as well as times of exacerbations. Data for asthma and COPD were then compared, and the risk factors for AEs were identified using logistic regression analysis.Results: A total of 251 patients were enrolled, comprising 162 (64.5%) who had asthma and 89 who had COPD, with none having COPD/asthma overlap. Frequency of AEs among asthma patients was significantly lower in 2020 than in 2019 (0.82 ± 3.33 vs. 1.00 ± 3.16; P < 0.05). Moreover, these patients visited the clinic less (0.37 ± 0.93 vs. 0.49 ± 0.94; P < 0.05) and used emergency drugs less (0.01 ± 0.11 vs. 007 ± 0.38; P < 0.05) during the COVID-19 pandemic. In contrast, among COPD patients, there were no significant differences in AE frequency, clinic visits, or emergency drug use. Furthermore, asthma patients visited clinics less frequently during the pandemic than those with COPD. Logistic regression analysis also showed that a history of at least one AE within the last 12 months was associated with increased AE odds for both asthma and COPD during the COVID-19 pandemic (odds ratio: 13.73, 95% CI: 7.04–26.77; P < 0.01).Conclusion: During the COVID-19 pandemic, patients with asthma showed better disease control than before, whereas patients with COPD may not have benefited from the pandemic. For both diseases, at least one AE within the previous 12 months was a risk factor for AEs during the pandemic. Particularly, among asthma patients, the risk factors for AE during the COVID-19 pandemic were urban environment, smoking, and lower asthma control test scores.

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows.

BackgroundThe risk of cancer treatment‐related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified.MethodsWe retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021.ResultsAmong the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment‐related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non‐AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment‐related AEs.ConclusionsLung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment‐related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

Current Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia.

Simple SummaryInterstitial pneumonia is a poor prognostic comorbidity in patients with non-small-cell lung cancer. No matter how effective the treatment for lung cancer is, once an acute exacerbation of pre-existing interstitial pneumonia occurs, it will be fatal to the patient at a high rate. Therefore, it is important to choose a therapy that is unlikely to induce acute exacerbation of interstitial pneumonia. In this review article, we summarize the current evidence on pharmacotherapy, surgery and perioperative treatment, and radiation therapy for non-small-cell lung cancer with comorbid interstitial pneumonia, and discuss future perspectives.Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP with cytotoxic drugs include honeycomb lungs on computed tomography (CT) and low forced vital capacity, but risk factors with immune checkpoint inhibitors (ICIs) have not been fully investigated. For advanced or recurrent NSCLC with comorbid IP, carboplatin plus nanoparticle albumin-bound paclitaxel is the standard of care for first-line treatment, but second-line or later treatment has not been established. ICI holds great promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Since the indications for pharmacotherapy and radiotherapy for NSCLC with comorbid IP are quite limited, surgical resection should be considered as much as possible for patients with operable stages. A scoring system has been reported to predict the risk of postoperative acute exacerbation of pre-existing IP, but perioperative treatment has not been established. In the future, it is necessary to accumulate more cases and conduct further research, not only in Japan but also worldwide.

The role of interleukin-6 as a prognostic biomarker for predicting acute exacerbation in interstitial lung diseases.

Interstitial lung diseases (ILDs) are chronic, parenchymal lung diseases with a variable clinical course and a poor prognosis. Within various clinical courses, acute exacerbation (AE) is a devastating condition with significant morbidity and high mortality. The aim of this study was to investigate the role of interleukin-6 (IL-6) to predict AE and prognosis in patients with ILD. Eighty-three patients who were diagnosed with ILD from 2016 to 2019 at the Haeundae Paik Hospital, Busan, South Korea, were included and their clinical data were retrospectively analyzed. The median follow-up period was 20 months. The mean age was 68.1 years and 65.1% of the patients were men with 60.2% of patients being ever-smokers. Among ILDs, idiopathic pulmonary fibrosis was the most common disease (68.7%), followed by connective tissue disease-associated ILD (14.5%), cryptogenic organizing pneumonia (9.6%), and nonspecific interstitial pneumonia (6.0%). The serum levels of IL-6 were measured at diagnosis with ILD and sequentially at follow-up visits. During the follow-ups, 15 (18.1%) patients experienced an acute exacerbation (AE) of ILD and among them, four (26.7%) patients died. In the multivariable analysis, high levels of IL-6 (OR 1.014, 95% CI: 1.001-1.027, p = 0.036) along with lower baseline saturations of peripheral oxygen (SpO2) were independent risk factors for AE. In the receiver operating characteristic curve analysis, the area under the curve was 0.815 (p < 0.001) and the optimal cut-off value of serum IL-6 to predict AE was 25.20 pg/mL with a sensitivity of 66.7% and specificity of 80.6%. In the multivariable Cox analysis, a high level of serum IL-6 (HR 1.007, 95% CI: 1.001-1.014, p = 0.018) was only an independent risk factor for mortality in ILD patients. In our study, a high level of serum IL-6 is a useful biomarker to predict AE and poor prognosis in patients with ILD.

Acute exacerbation of fibrotic hypersensitivity pneumonitis: incidence and outcomes

BackgroundPatients with fibrotic hypersensitivity pneumonitis (HP) show variable clinical courses, and some experience rapid deterioration (RD), including acute exacerbation (AE). However, little is known about AE in fibrotic HP. Here, we retrospectively examined the incidence, risk factors, and outcomes of AE in fibrotic HP.MethodsThe incidence rates of AE were calculated in 101 patients with biopsy-proven HP. AE was defined as the worsening of dyspnoea within 30 days, with new bilateral lung infiltration and no evidence of infection or other causes of dyspnoea.ResultsDuring follow-up (median: 30 months), 18 (17.8%) patients experienced AE. The 1, 3, and 5 year incidence rates of AE were 6.0, 13.6, and 22.8%, respectively. Lower diffusing capacity of the lung for carbon monoxide (DLCO) and a radiologic usual interstitial pneumonia (UIP)-like pattern were risk factors for AE. In-hospital mortality after AE was 44.4%. Median survival from diagnosis was significantly shorter in patients with AE (26.0 months) than in those with no-AE RD (55.0 months; p = 0.008) or no RD (not reached; p < 0.001). AE remained a significant predictor of all-cause mortality (hazard ratio, 8.641; 95% confidence interval, 3.388–22.040; p < 0.001) after adjustment for age, body mass index, lung function, lymphocyte levels in bronchoalveolar lavage fluid, and the presence of a UIP-like pattern.ConclusionsAE was not uncommon among patients with fibrotic HP and significantly affected prognosis. A lower DLCO value and radiologic UIP-like pattern at diagnosis were associated with the development AE in patients with fibrotic HP.

Risk factors for acute exacerbation following bronchoalveolar lavage in patients with suspected idiopathic pulmonary fibrosis: A retrospective cohort study.

Bronchoalveolar lavage (BAL) is useful for diagnosing diffuse lung disease and excluding other conditions. However, acute exacerbations (AEs) are recognized as important complications of BAL in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to identify risk factors for BAL-induced AEs in patients with IPF. We retrospectively analyzed the data of 155 patients with suspected IPF who had undergone BAL between January 2013 and December 2018. BAL-related AE was defined as the development of AE within 30 days after the procedure. We compared clinical features and parameters between patients with AE (AE group) and without AE (non-AE group). We also reviewed the relevant reported literature. Among the 155 patients, 5 (3.2%) developed AE within 30 days after BAL. The average duration from BAL to AE onset was 7.8 days (2-16 days). Results from the univariate analysis revealed PaO2 < 75 mm Hg (p = 0.036), neutrophil content in BAL ≥ 7% (p = 0.0061), %DLCO < 50% (p = 0.019), Gender-Age-Physiology (GAP) stage III (p = 0.034), and BAL recovery rates < 30% (p < 0.001) as significant risk factors for post-BAL AE. All five patients who developed AE recovered and were discharged. Disease severity, high neutrophil levels in BAL, and poor BAL recovery rates may be risk factors for BAL-induced AEs.

Exposure to PM2.5 is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case\u2013control study

BackgroundShort-term exposure to ozone and nitrogen dioxide is a risk factor for acute exacerbation (AE) of idiopathic pulmonary fibrosis (AE-IPF). The comprehensive roles of exposure to fine particulate matter in AE-IPF remain unclear. We aim to investigate the association of short-term exposure to fine particulate matter with the incidence of AE-IPF and to determine the exposure-risk time window during 3 months before the diagnosis of AE-IPF.MethodsIPF patients were retrospectively identified from the nationwide registry in Japan. We conducted a case–control study to assess the correlation between AE-IPF incidence and short-term exposure to eight air pollutants, including particulate matter < 2.5 µm (PM2.5). In the time-series data, we compared monthly mean exposure concentrations between months with AE (case months) and those without AE (control months). We used multilevel mixed-effects logistic regression models to consider individual and institutional-level variables, and also adjusted these models for several covariates, including temperature and humidity. An additional analysis with different monthly lag periods was conducted to determine the risk-exposure time window for 3 months before the diagnosis of AE-IPF.ResultsOverall, 152 patients with surgically diagnosed IPF were analyzed. AE-IPF was significantly associated with an increased mean exposure level of nitric oxide (NO) and PM2.5 30 days prior to AE diagnosis. Adjusted odds ratio (OR) with a 10 unit increase in NO was 1.46 [95% confidence interval (CI) 1.11–1.93], and PM2.5 was 2.56 (95% CI 1.27–5.15). Additional analysis revealed that AE-IPF was associated with exposure to NO during the lag periods lag 1, lag 2, lag 1–2, and lag 1–3, and PM2.5 during the lag periods lag 1 and lag 1–2.ConclusionsOur results show that PM2.5 is a risk factor for AE-IPF, and the risk-exposure time window related to AE-IPF may lie within 1–2 months before the AE diagnosis. Further investigation is needed on the novel findings regarding the exposure to NO and AE-IPF.