Occurrence Of Acute Exacerbations Research Articles

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy’s effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25–8.8). Median survival time was 9.9 months (95% CI 9.2–10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889–9.328; 60 days, HR: 2.351, 95% CI 1.104–5.009; 90 days, HR: 2.416, 95% CI 1.232–4.739; and 120 days, HR: 2.521, 95% CI 1.357–4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

The current status of reversal therapy in Japan for elderly patients with head injury treated with antithrombotic agents: A prospective multicenter observational study

BackgroundAcute exacerbation of head injury in elderly patients due to use of antithrombotic agents has become a concern in countries with aging populations. Reversal agents are recommended for treatment, but its usage is unclear. Therefore, we conducted a prospective observational study in this patient population to monitor usage of reversal therapy. MethodsThe subjects were 721 elderly patients aged ≥65 years old who were hospitalized in 15 centers from December 2019 to May 2021. Patients were divided into groups who did not receive antithrombotic agents (Group A), who received antithrombotic agents, but did not receive reversal therapy (Group B), and were treated with antithrombotic agents and reversal therapy (Group C). Age, gender, mechanism of injury, neurologic and imaging findings on admission, clinical course after admission and surgery, outcomes and complications were compared among these groups. Time from injury to reversal therapy was examined based on outcomes to investigate trends in the timing of administration of the reversal agent. ResultsAcute exacerbation during the clinical course occurred in 9.8 %, 15.8 % and 31.0 % of cases in Groups A, B and C, respectively, and differed significantly among the groups. On head CT, the incidences of hematoma were 35.7 %, 36.5 % and 60.4 %, respectively, with this incidence being significantly higher in Group C; and the respective rates of craniotomy were 18.8 %, 14.0 % and 50.9 %, again with this rate being significantly higher in Group C. The good outcome and mortality rates were 57.1 %, 52.5 % and 35.8 %, and 14.5 %, 18.0 % and 24.5 %, respectively, and both were poorest in Group C. Times from injury to treatment with a reversal agent were significantly shorter in patients without compared to those with acute exacerbation (405.9 vs. 880.8 min) and in patients with favorable outcomes compared to those with unfavorable outcomes (261.9 vs. 543.4 min). ConclusionSimilarly to previous studies, the incidence of acute exacerbation was increased by use of antithrombotic agents. These results suggest that patients in Japan who require hematoma evacuation due to symptom exacerbation tend to be treated with reversal agents. Although it is difficult to assess the efficacy of reversal therapy from this study, earlier treatment with reversal agents before the occurrence of acute exacerbation may be useful to improve outcomes.

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study

ObjectiveInterstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease.MethodsThis study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables.ResultsElevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = − 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = − 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker.ConclusionsElevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

Interleukin-11 in idiopathic pulmonary fibrosis: predictive value of prognosis and acute exacerbation.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and unknown aetiology. We have recently clarified the prognostic value of the serum platelet-derived growth factor (PDGF) level in patients with IPF. Interleukin (IL)-11 is a member of the IL-6 family, and in vivo and in vitro studies have suggested that it has profibrotic effects in pulmonary fibrosis. In this study, we investigated the predictive value of the serum IL-11 level in patients with IPF for survival and occurrence of acute exacerbation (AE). This retrospective study included 68 patients with IPF diagnosed according to the 2018 guideline. Serum PDGF levels were measured using the Bio-Plex method and serum IL-11 levels using enzyme-linked immune-sorbent assay. Cytokine production per lung volume was evaluated using the serum cytokine/percent predicted forced vital capacity (%FVC) value. Forty-six patients were male and the median age was 67 years. The serum IL-11/%FVC value was significantly correlated with the percent predicted diffusing capacity of carbon monoxide (ρ=-0.518, P<0.001) and modified Medical Research Council score for shortness of breath (mMRC) (ρ=0.335, P=0.006) by Spearman's rank correlation analysis. Multivariate Cox proportional hazard regression analysis revealed that the serum IL-11/%FVC value was a significant prognostic factor after adjustment for the serum PDGF/%FVC value and other clinical parameters including mMRC and lymphocyte percentage in bronchoalveolar lavage [hazard ratio (HR): 88.540, 95% confidence interval (CI): 1.905-4,115.686, P=0.022]. IL-11/%FVC value was also a significant predictor of AE after adjustment for age and PDGF/%FVC (HR: 1,815.443, 95% CI: 10.49-314,109.219, P=0.004). The serum IL-11/%FVC value was an independent predictor of prognosis and AE occurrence in patients with IPF, and the IL-11 level appeared to show pathophysiologic value in IPF.

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.

Patient and Health Care Provider Perspectives on Potential Preventability of Hospital Admission for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Qualitative Study.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic disease partly characterised by the occurrence of acute exacerbations (AECOPD). The need for hospital admissions for COPD exacerbations could theoretically be decreased through timely and appropriate outpatient care or self-management. The aim of this study is to explore and compare patients' and health care providers' (HCP) perspectives on the potential preventability of COPD hospitalisations and to identify strategies to prevent unnecessary hospitalisations. Semi-structured interviews were conducted with patients admitted for an AECOPD (N = 11), HCPs on the respiratory ward (N = 11), and treating pulmonologists (N = 10). Interviews were transcribed verbatim and analysed using thematic content analysis. Patient and HCP perspectives on the potential preventability of hospital admissions for AECOPD often conflict. The kappa coefficients were -0.18 [95% CI: -0.46-0.11] for patients and pulmonologists and -0.28 [95% CI: -0.80-0.21] for patients and HCPs, which indicates poor agreement. The kappa coefficient for pulmonologists and HCPs was 0.14 [95% CI: -0.13-0.41], which indicates slight agreement. Patient and HCP factors that could potentially prevent hospitalisation for AECOPD were identified, including timely calling for help, recognizing and acting on symptoms, and receiving instruction about COPD, including treatment and action plans. Patients and their HCPs have different beliefs about the potential preventability of AECOPD hospitalisations. Most patients and HCPs mentioned factors that potentially could have led to a different outcome for the current AECOPD or that could impact the patient's health status and treatment of AECOPDs in the future. The factors identified in this study indicate that shared decision making is crucial to center the patient's perspective and individual needs and to provide timely treatment or prevention of AECOPD, thereby potentially decreasing hospital admission rates.

Diagnostics of Interstitial Lung Diseases - Practical Instructions with a Focus on Rheumatologic Systemic Diseases

Interstitial lung diseases (ILD) are etiologically heterogeneous with unknown and known causes like rheumatologic systemic diseases differing in their therapeutic and prognostic consequences. In consensus between pulmonologists, rheumatologists, radiologists, and pathologists, we developed practical instructions for ILD diagnosis in rheumatologic systemic diseases, in particular because ILD can present in early stages of rheumatic systemic diseases. ILD diagnosis is based on clinical assessment results including a detailed medical history, physical examination, focused laboratory tests, radiology with a high-resolution computed tomography, lung function, and histopathology also to differentiate it from cardiac and infection associated lung diseases. The ILD diagnosis is made in a multidisciplinary discussion leading to therapeutic and prognostic consequences. The occurrence of acute exacerbations is especially critical. They are often the causes for ILD progression and are associated with considerable mortality.

Complications and Survival After Lung Cancer Resection in Interstitial Lung Disease

BackgroundIdiopathic pulmonary fibrosis guidelines changed the high-resolution computed tomography (HRCT) pattern from 3 to 4 categories in 2018. We assessed the relationship between surgical outcomes and HRCT patterns according to the 2018 guidelines. MethodsAmong 1503 patients who underwent pulmonary resection for clinical stage Ⅰ to stage Ⅲ lung cancer at our institution between April 2007 and June 2019, we retrospectively investigated 218 with interstitial lung abnormalities based on preoperative HRCT. We reclassified all interstitial lung abnormality cases with preoperative HRCT from 3 patterns—usual interstitial pneumonia (UIP), possible, and inconsistent with UIP—of the previous (2011) guidelines to 4 patterns—UIP, probable UIP, indeterminate, and alternative diagnosis—according to the new consensus guideline of idiopathic pulmonary fibrosis (2018). The occurrence of acute exacerbations and survival were analyzed, and the association with HRCT pattern was investigated. ResultsInterstitial lung abnormality cases were reclassified as UIP (n = 55 [25.2%]), probable UIP (n = 36 [16.5%]), indeterminate UIP (n = 56 [25.7%]), and alternative diagnosis (n = 71 [32.6%]). Acute exacerbations developed in 21 patients (UIP pattern, n = 9 [16.4%]; probable UIP, n = 5 [13.9%]; indeterminate, n = 3 [5.4%]; and alternative diagnosis, n = 4 [5.6%]). Multivariable Cox regression revealed that UIP pattern or probable UIP pattern of the 2018 guideline was an independent risk factor for severe acute exacerbations (grade III-Ⅴ; odds ratio, 6.81; 95% CI, 1.42-32.60) and postoperative overall survival (hazard ratio, 3.12; 95% CI, 1.70-5.73). ConclusionsUIP and probable UIP patterns were risk factors for postoperative severe acute exacerbations and death. The HRCT patterns of the 2018 guidelines can stratify outcomes of lung resection.

Acute Respiratory Deterioration in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Single-Center Study

Interstitial lung disease (ILD) is associated with increased morbidity and mortality in rheumatoid arthritis (RA). Moreover, acute exacerbation (AE) is a devastating complication of RA plus ILD. However, few data on AE in RA-associated ILD are available. What are the incidence, risk factors, and outcomes of AE in patients with RA-associated ILD? The clinical data of 310 patients with RA-associated ILD were analyzed retrospectively. AE was defined as the acute worsening of dyspnea typically within 30days with new bilateral lung infiltration, which was based on a 2016 report by an international working group. The mean age of the participants was 61.9 years, and 56.2%of them were women. During follow-up (median, 47.7months), AE occurred in 87 patients (28.1%). The 1-year, 3-year, and 5-year cumulative incidence rates of AE in patients with RA-associated ILD were 9.2%, 19.8%, and 29.4%, respectively. Ever smoker status, lower FVC, and shorter 6-min walk distance were significant risk factors for the occurrence of AE. In the multivariate Cox analysis adjusted by age, sex, smoking status, lung function, exercise capacity, and high-resolution CT scan pattern, AE was a significant prognostic factor for overall survival (hazard ratio, 2.423; 95%CI, 1.605-3.660; P< .001) in patients with RA-associated ILD. The 30-day and 90-day mortalities after AE were 12.6%and 29.9%, respectively. Our findings suggest that approximately one-third of patients with RA-associated ILD experience AE and that ever smoker status, and lower lung function and exercise capacity predispose patients to AE. AE significantly affects the overall survival of patients with RA-associated ILD.

Association between influenza vaccination and the occurrence of acute exacerbation inidiopathic pulmonary fibrosis

International guidelines recommend that annual influenza vaccination be performed in patients with idiopathic pulmonary fibrosis (IPF). Viral infections are recognized to be triggers of acute exacerbation (AE). The purpose of this study was to investigate the role of annual influenza vaccination on AE occurrence. 236 patients with incident IPF were included in the multicentric longitudinal prospective cohort COhorte FIbrose (COFI), and followed for 5 years. Influenza vaccination status was requested annually. We have defined aone-year vaccination coverage from September the first to August the 30th of the following year. 638 annual observations were available with an informed vaccination status. To evaluate the association between annual influenza vaccination and AE occurrence, two mixed-effect Cox regression was used. For the second model we divided patients in 3 groups: – patients vaccinated every year; – patients vaccinated at least half of the years of follow-up; – patients vaccinated less than half the years of follow-up. Only the first AE was considered. The definition of AE was that of Akira et al. Mean follow-up was 33.2 ± 23.6 months. 36 AEs occurred in 33 patients. Of the 33 patients, only 27 had an informed vaccination status in the year of their AE. Nine (33%) patients who experienced an AE weren’t vaccinated. For 141 (22%) annual observations, the patient didn’t receive the vaccine. In this model, influenza vaccination was associated with a decreased occurrence of AE but this did not reach the level of significance in this small population (HR:0.58 CI95%0.23-1.46, P = 0.25). In the first group patients were vaccinated every year and consisted of hundred and thirty-three individuals. The second group was composed of patients vaccinated at least half of the years of follow-up, with 35 patients. And 36 patients were vaccinated less than half the years of follow-up in the last group. In the second model, patients vaccinated less than half the years of follow-up were significantly more at risk to present AE compared to patients who were vaccinated every year (HR:2.77 CI95%1.11-6.93, P = 0.03). In our IPF cohort, only about half of the patients had influenza vaccination coverage throughout the follow-up period. Annual influenza vaccination seems to reduce the risk of AE but due to a lack of power this association was not significant. However patients vaccinated less than half the years of follow-up were significantly more at risk to present AE compared to patients who were vaccinated every year. A study with a larger number of patients is highly desirable to confirm this association.

Influence de l´intensité de l´intoxication tabagique sur les paramètres de sévérité des exacerbations aigues de la broncho-pneumopathie chronique obstructive traitées en milieu hospitalier

Introductionle tabagisme constitue le principal facteur de risque de la broncho-pneumopathie chronique obstructive (BPCO). Le cours évolutif de cette maladie est caractérisé par la survenue des exacerbations aiguës (EA). L'objectif de notre travail est d'évaluer l´impact de l´intensité de l´intoxication tabagique (en paquets-années (PA)) sur les différents paramètres de sévérité des EA des patients BPCO non sevrés hospitalisés.Méthodesc´est une étude rétrospective, monocentrique, portant sur 685 patients porteurs de BPCO, tabagiques non sevrés ayant été hospitalisés au moins une fois pour une EA entre 1990 et 2017. Nous avons défini 2 groupes de patients (G1: < 30PA, et G2: ≥ 30PA). Nous avons comparé les différents paramètres de sévérité des EA BPCO entre les deux groupes.Résultatsl´âge moyen de nos patients était de 66 ans. Il n'y avait pas de différence significative entre les deux groupes concernant l´importance du syndrome inflammatoire biologique, la durée de l´hospitalisation et celle de l´antibiothérapie. Le G2 était caractérisé par une PaO2 plus basse au cours des EA (G1: 63,5, G2: 59,3, p: 0,007), avec plus d'hospitalisation en réanimation (p < 0,001), plus de recours à la ventilation non invasive (p: < 0.001) et à la ventilation invasive (p: 0,008). Le G2 avait plus d'EA/an (G1: 2,06, G2: 2,72/patient/an, p: 0,001) avec un délai moyen de survenue d'EA sévère plus court (p: 0,038).Conclusionl´intensité de l´intoxication tabagique a un impact négatif sur plusieurs paramètres de sévérité des EA sévères de BPCO. D´où l´intérêt de sevrage tabagique pour prévenir la maladie et ses complications.

Prevalence of influenza and pneumococcal vaccination in chronic obstructive pulmonary disease patients in association with the occurrence of acute exacerbations.

BackgroundBased on current evidence, vaccination is recommended against the influenza virus and pneumococcus to avoid serious acute exacerbations in patients with chronic obstructive pulmonary disease (COPD), but the rate of their vaccination coverage is still suboptimal. To determine the prevalence and effectiveness of influenza and pneumococcal vaccination in COPD patients, and to prove its hypothetical association with the decreasing number of acute exacerbations.MethodsWe conducted a retrospective, population-based cohort study. Influenza and pneumococcal vaccination history were collected from 250 patients selected by simple random sampling from all COPD patients in Budapest at the Department of Pulmonary Rehabilitation of the National Koranyi Institute of Pulmonology between 01 January 2019 and 01 June 2019. Inclusion criteria were the following: age 40 years and diagnosis of COPD. Odds ratios (ORs) were evaluated based on the occurrence of acute exacerbations during the preceding year.ResultsThe average age was 66.62 (±8.34) years, 67.30 (±8.54) for males, and 66.09 (±8.16) for females. Man:woman ratio: 43.6%:56.4% in total. Overall prevalence of influenza vaccination was 23.6%, and the pneumococcal vaccination rate was 10.8% among COPD patients. Influenza and pneumococcal vaccination showed a significant protective effect and reduced the occurrence of exacerbations in the following year, influenza vaccination OR: 2.11 (95% CI: 0.88–5.02), pneumococcal vaccination OR: 1.06 (95% CI: 0.84–1.34), when taking both vaccination: OR: 2.37 (95% CI: 1.39–4.08).ConclusionsWe found association between influenza and pneumococcal vaccination and the reduced risk of hospitalization due to exacerbations in the ensuing year. The prevalence of vaccination is significantly below the optimal level.

Association Between Adherence to Maintenance Medication in Patients with COPD and Acute Exacerbation Occurrence and Cost in China: A Retrospective Cohort Database Study.

BackgroundThis study aimed to evaluate the association between adherence to maintenance medication (ie, inhaled bronchodilators, inhaled corticosteroid/long-acting beta-2 agonist [ICS/LABA] combinations, and oral therapy) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and related costs among patients with chronic obstructive pulmonary disease (COPD) in China.Patients and MethodsClaims data from the hospitals of a metropolitan city in south China between January 2014 and December 2016 were obtained. Patients with COPD with ≥2 maintenance medication claims during 1 year were included. Adherence was measured by the proportion of days covered (PDC). The interaction of medication class×adherence was considered when building models.ResultsA total of 11,708 patients met the inclusion criteria, of whom 10.8% were highly adherent (PDC≥0.8). There were significant interaction effects of drug category on hospitalized AECOPD risk (P≤0.001), hospitalized AECOPD rate (P<0.001), and 1-year hospitalized AECOPD treatment costs (P=0.012). There was a relationship between high adherence and outcomes for ICS/LABA combinations (n=3,419), ie, relative risk of hospitalized AECOPD was reduced by 34.8% (adjusted odds ratio=0.65; 95% confidence interval (CI): 0.54–0.79; P<0.001) while the frequency of hospitalized AECOPD per patient-year was reduced by 24.4% (adjusted rate ratio=0.76; 95% CI: 0.65 to 0.87; P<0.001). Mean 1-year per-patient hospitalized AECOPD costs were reduced by 37.8% (mean difference=−848 USD; 95% CI: −1435–262 USD; P<0.001). Patients taking oral mucolytics and having high adherence had worse AECOPD outcomes than patients with poor adherence.ConclusionHigh adherence to ICS/LABA maintenance therapy was associated with reduced hospitalized AECOPD rates and costs in Chinese patients with COPD.

Health-related quality of life and symptoms in patients with IPF treated with nintedanib: analyses of patient-reported outcomes from the INPULSIS\xae trials

BackgroundIn the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George’s respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression.MethodsPatient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DLCO] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test.ResultsData from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DLCO ≤ 40%, CPI > 45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores).ConclusionsIn patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.

Real-life experiences in a single center: efficacy of pirfenidone in idiopathic pulmonary fibrosis and fibrotic idiopathic non-specific interstitial pneumonia patients.

Background:Pirfenidone is the first antifibrotic drug approved for the treatment of idiopathic pulmonary fibrosis (IPF) and it is used in the treatment of other interstitial pneumonias, such as unclassifiable interstitial lung disease (ILD) and connective tissue-related ILD. This study examined the efficacy of pirfenidone in patients with IPF and fibrotic idiopathic non-specific interstitial pneumonia (f-iNSIP).Methods:In a retrospective real-life study, 67 IPF and 24 f-iNSIP patients were enrolled and classified into a pirfenidone group and a non-antifibrotic group. The level of forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLco) at baseline, 6, 12 and 24 months were recorded. The level of KL-6 in serum was detected by chemiluminescence enzyme immunoassay (CLEIA). The prognosis and safety outcomes were collected from patients.Results:In IPF patients, pirfenidone decreased the mean change of FVC and DLco, and decreased the proportion of patients with a ⩾10% decline in FVC or a ⩾15% decline in DLco compared with the non-antifibrotic group. There was no difference in the mean change of FVC and DLco between smokers and non-smokers who received pirfenidone treatment. There was an improvement in progression-free survival, defined as the time to the first occurrence of acute exacerbation or death related to pulmonary fibrosis. Moreover, the ratio of patients who experienced acute exacerbation and death related to pulmonary fibrosis was lower in the pirfenidone group. There was no change in lung function and prognosis between the pirfenidone and non-antifibrotic groups in f-iNSIP patients. The KL-6 level slightly decreased after 1 year of pirfenidone treatment but not significantly. Gastrointestinal and skin-related adverse events were most common, and four patients ceased treatment due to the side effects.Conclusions:Pirfenidone safely reduced disease progression by improving the lung function and progression-free survival in IPF patients, with acceptable side effects. The efficacy of pirfenidone on f-iNSIP was not significant, suggesting the need for further studies.The reviews of this paper are available via the supplemental material section.

P1.16-25 Impact of Pirfenidone on the Risk Scoring System of Postoperative Acute Exacerbation of Interstitial Pneumonia in Lung Cancer

Acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) is a life-threatening complication of lung cancer resection. There has been an increasing number of studies about postoperative AE of IIP in recent years. A few of these have reported that perioperative oral administration of pirfenidone reduces the occurrence of AE in patients with IIP. Furthermore, a large cohort study conducted by the Japanese Association for Chest Surgeons (JACS) proposed risk factors for postoperative AE in IIP patients which can predict the incidence of AE following an operation. JACS risk score included seven factors (sex, history of AE, surgical procedure, usual interstitial pneumonia pattern, steroid use, KL-6, %VC) and classified patients into three groups: low risk (risk score: 0-10), intermediate risk (risk score: 11-14) and high risk (risk score: 15-22). The objective of present study is to investigate the validity of those risk factors for patients with IIP who are taking pirfenidone. We retrospectively analyzed 1626 consecutive lung cancer patients who had undergone lung resection at our institution from January 2010 to December 2018. The patients who underwent lung resection since 2016 onward were administered pirfenidone from 4 weeks before operation to 4 weeks after operation. Out of 1626 patients, 125 patients (7.7%) had IIP. Twenty patients (16%) took pirfenidone and 105 patients (84%) did not take pirfenidone. Of the patients taking pirfenidone, three patients (15%) contracted AE of IIP after lung resection within 30 postoperative days. No significant difference was identified in JACS risk score between AE (+) group taking pirfenidone and AE (-) group taking pirfenidone (10.7 ± 3.2 versus 8.6 ± 2.6, p = 0.74). In the AE (+) group taking pirfenidone, there were significant higher rates of patients having increased serum levels of KL-6 or having reached pathological stage II-IV (UICC 8th) (p = 0.01 , p = 0.04, respectively). Of the patients not taking pirfenidone, seven patients (6.7%) contracted AE of IIP. No significant difference was identified in incidence of postoperative AE between the group of patients taking pirfenidone and the group not taking pirfenidone (p = 0.21). In the patients taking pirfenidone, there was no significant difference in the risk score between AE (+) group and AE (-) group.

Prognostic value of IFN-γ, sCD163, CCL2 and CXCL10 involved in acute exacerbation of idiopathic pulmonary fibrosis

ObjectiveAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is of concern because of its propensity for rapid deterioration and high mortality. Its aetiology and mechanism are still unclear. The aims of this study were to clarify the pathophysiology differences between AE-IPF and stable IPF (S-IPF) by comparing the serum levels of various cytokines and chemokines in the two groups and to identify those involvement in the occurrence of acute exacerbation and associated with mortality. MethodsThe study included 28 patients with AE-IPF, 32 patients with S-IPF, and 18 healthy control subjects. We measured the serum cytokine and chemokine levels in all cases by multiplex assay. Serum levels of cytokines and chemokines were compared between AE-IPF and S-IPF subjects. Logistic regression analysis was applied to identify the ability of these variables to predict acute exacerbation. Kaplan-Meier curves were used to analyse survival and Cox proportional hazard regression was used to identify predictors of survival. ResultsLevels of several cytokines and chemokines were significantly higher in both patient groups with IPF (with the exception of interleukin-2 [IL-2], chemokine cc-motif ligand 3, and RANTES [regulation upon activation normal T-cell express sequence]) than in healthy controls. Serum IL-1β (p = 0.008) and interferon (IFN)-γ (p = 0.007) levels tended to be higher in patients with AE-IPF than in those with S-IPF. The concentration of chemokine cc-motif ligand (CCL) 2 was significantly higher in bronchoalveolar lavage fluid than in serum (p = 0.001). Higher C-reactive protein, lactate dehydrogenase, percent forced vital capacity, percent diffusing capacity of the lung for carbon monoxide, and IFN-γ values in the patients with IPF were correlated with acute exacerbation status, with respective odds ratios of 1.241 (p = 0.011), 1.050 (p = 0.004), 1.043 (p = 0.001), 0.927 (p = 0.014), and 0.929 (p = 0.020). Acute exacerbation status was associated with an increased risk of mortality (hazard ratio 0.107, 95% confidence interval 0.036–0.314; p < 0.001). Univariate Cox regression demonstrated an association of IFN-γ, CCL2, C-X-C motif chemokine 10 (CXCL10) and sCD163 levels with an increased mortality risk (p = 0.015, p = 0.002, p = 0.001, and p = 0.030, respectively). ConclusionsOur data demonstrate that serum levels of some pro-inflammatory cytokines and macrophage chemokines are upregulated during acute exacerbations of IPF and that these exacerbations are associated with the serum IFN-γ level. Chemokines and protein such as sCD163, CCL2, and CXCL10 are associated with activation of macrophages and may have a serious impact on overall survival in patients with IPF.

Treatment of allergic rhinitis reduces acute asthma exacerbation risk among asthmatic children aged 2-18 years.

Asthma and allergic rhinitis (AR) frequently coexist in the same individuals in childhood and adolescence. We evaluated whether AR had an impact on acute exacerbation (AE) and whether intranasal corticosteroid (INCS) and second-generation antihistamines (SGH) for AR modified the association of AR with AE in asthmatics aged 2-6 years and 7-18 years. Using the National Health Research Institutes (NHRI) Database 2005 of Taiwan, we investigated patients who had been diagnosed with asthma in the years 2000 through 2012 and who had then been followed-up with for at least one year. The risk factors of AE were evaluated using multiple Cox proportional hazards regression analysis. The incidence of AE was higher in the preschool group than the older group (adj. HR: 1.68, 95% CI: 1.44-1.95). The AR with INCS and/or SGH group was found to have a lower risk of AE than the non-AR group (adj. HR: 0.32, 0.44 and 0.30), but the AR without treatment group did not have a significant difference with the non-AR group. After propensity score matching, the use of INCS and/or SGH was associated with a significant reduction in the occurrence of AE among AR patients aged 2-6 years old (adj. HR: 0.38, 0.57 and 0.45) and 7-18 years old (adj. HR: 0.50, 0.52 and 0.35). The preschool patients had a higher incidence of AE than the older patients in general. Adequate treatment with INCS and/or SGH in asthma with AR patients is important for reducing the incidence of AE of asthma.

Clinico-radio-pathological characteristics of unclassifiable idiopathic interstitial pneumonias.

The purpose of this study was to clarify the clinico-radio-pathological characteristics and prognostic factors of unclassifiable-idiopathic interstitial pneumonias (U-IIPs) diagnosed by surgical lung biopsy. Among 86 patients with interstitial pneumonia who underwent surgical lung biopsy from January 2005 to September 2013, 33 (38.4%; 16 male patients; mean age, 64.4 ± 8.8 years) were diagnosed with U-IIPs. They were subsequently categorized into rapidly progressive (n = 7), slowly progressive (n = 7), and stable (n = 19) groups based on the decrease of the percent predicted forced vital capacity or percent predicted diffusing capacity of the lung carbon monoxide and the occurrence of acute exacerbation. The clinico-radio-pathological features and survival rates of the patients who were followed up for at least 3 years were examined. These cases were reevaluated retrospectively by multidisciplinary discussion. The rapidly progressive group had a significantly poorer prognosis than that of the other groups (p < 0.0001). Although there were no significant pattern differences on the chest high-resolution computed tomography, the fibrosis scores were significantly higher in the rapidly progressive group (p = 0.002). Furthermore, the percentage of fibroblastic foci assessed by the pathological analysis was also significantly higher in the rapidly progressive group (p = 0.006). Nine (27.3%) patients developed connective tissue diseases during follow-up. The radiologic patterns were not significantly different among the three clinical U-IIPs subgroups. Nevertheless, our findings suggested that the fibrosis scores and the percentage of fibroblastic foci could provide a prognostic assessment in U-IIPs.