Disease trajectories in interstitial lung diseases - data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5-10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression. RESULTS: Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001). CONCLUSION: Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection. RESULTS: In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005). CONCLUSION: Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted.

Effect of the novel dual orexin receptor antagonist daridorexant on night-time respiratory function and sleep in patients with moderate chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), sleep is often fragmented while, conversely, the use of sleep medications is of concern in these patients due to potential impairment of nocturnal breathing. This randomised, double-blind, placebo-controlled, two-period crossover study was conducted to evaluate the effect of the new dual orexin receptor antagonist daridorexant on night-time respiratory function and sleep in patients with moderate COPD. In each period, the highest Phase-III dose of 50 mg daridorexant or placebo was administered once daily in the evening for 5 consecutive days. The primary endpoint was peripheral oxygen saturation (SpO2 ) during total sleep time (TST) after last dosing. Night-time respiratory function and sleep were further evaluated based on the apnea-hypopnea index (AHI), sleep duration, and objective sleep parameters. Pharmacokinetics, safety, and tolerability were also assessed. Primary endpoint analysis revealed no significant mean treatment difference (i.e. daridorexant - placebo) for SpO2 during TST as it was 0.18% (90% confidence interval: -0.21 to 0.57). There was also no difference from placebo for SpO2 during non-rapid eye movement (REM) and REM sleep at Night 5 and after first dosing. The AHI was slightly increased compared to placebo, but not to a clinically meaningful extent. In addition, daridorexant improved objective sleep parameters (i.e. prolonged TST, increased sleep efficiency, and decreased wake after sleep onset), reached expected plasma concentrations, and was safe and well tolerated. In conclusion, single and multiple doses of 50 mg daridorexant do not impair night-time respiratory function and improves sleep in patients with moderate COPD.

Tratamiento endoscópico de las estenosis benignas traqueobronquiales tipo web-like con el bisturí endobronquial en combinación con un programa de corte optimizado / The Electrosurgical Knife in an Optimized Intermittent Cutting Mode for the Endoscopic Treatment of Benign Web-Like Tracheobronchial Stenosis

El tratamiento endoscópico establecido de las estenosis traqueobronquiales tipo web-like es el láser. La aparición en el mercado de un nuevo modo de corte con un menor efecto coagulante se ha postulado como una alternativa al láser debido a un menor daño en los tejidos afectados. Objetivos: Estudiar las consecuencias clínicas, funcionales y los efectos secundarios de esta técnica y posteriormente compararla con un grupo similar de pacientes tratados con láser ND-YAG. Pacientes y método: Entre marzo del 2005 y julio del 2007 se incluyeron 22 pacientes que fueron sometidos a 34 procedimientos de broncoscopia intervencionista mediante el sistema de radiofrecuencia VIO-300-D, usando un modo el programa Endo-cut I en combinación con el electrodo de cuchilla reutilizable. Resultados: El 100% de los pacientes tratados presentaron mejorías de los síntomas, del diámetro de la luz traqueobronquial y de la función pulmonar que fueron estadísticamente significativas. El tiempo libre de síntomas fue de 157±93 días, y menos del 50% de los pacientes necesitaron una segunda intervención. Retrospectivamente, se compararon estos pacientes con un grupo similar de 22 pacientes tratados con el láser Nd-YAG. El análisis de seguimiento mostró que solo el 18% (4/22) de los pacientes tratados con esta nueva técnica presentaron fibrina, en comparación con el 41% (9/22) de los tratados con láser (p<0,001). Conclusión: El uso de esta técnica es eficaz en el tratamiento de las estenosis benignas traqueobronquiales tipo web-like ya que todos los pacientes mostraron mejoría clínica y funcional, requiriendo menos del 50% una segunda intervención. En comparación con el láser, una ventaja de esta técnica es la menor producción de fibrina, probablemente debido a su menor efecto anticoagulante(AU)

The established endoscopic treatment of web-like tracheobronchial stenosis is laser vaporization, but the appearance on the market of a new cutting mode with a lower coagulation effect has been proposed as an alternative to laser due to less injury to the tissue. Objectives: To study the clinical and functional consequences, as well as the side effects of this technique. Afterwards, we investigated whether the use of an electrosurgical knife with this technique is as effective and convenient as an ND-YAG-laser. Patients and methods: Between March 2005 and July 2007, included for study were 22 patients who had undergone 34 interventional bronchoscopy procedures with the VIO-300-D radiofrequency system, using a mode of the Endo-cut I program in conjunction with the reusable knife electrode. Results: All of the patients treated (100%) presented improvements in their symptoms, in the tracheobronchial lumen diameter and in lung function, which were statistically significant. Symptom-free time was 157±93 days. There was an overall decrease observed in mean obstruction (P<.001). Improvements in FVC (P=.01), Raw (P=.0016) and RV/TLC (P=.01) were significantly significant. Less than 50% of the patients needed a second intervention. These patients were compared retrospectively with a similar group of 22 patients treated with Nd-YAG laser. The follow-up analysis showed that only 18% (4/22) of the patients treated with this new technique presented fibrin, compared with 41% (9/22) of those treated with laser therapy (P<.001). Conclusion: The use of this technique is effective for the treatment of benign web-like tracheobronchial stenosis as all the patients showed clinical and functional improvement, and less than 50% required a second intervention. In comparison with laser therapy, an advantage of this technique is that less fibrin is produced, probably due to the reduced anticoagulation effect(AU)

The electrosurgical knife in an optimized intermittent cutting mode for the endoscopic treatment of benign web-like tracheobronchial stenosis.

UNLABELLED: The established endoscopic treatment of web-like tracheobronchial stenosis is laser vaporization, but the appearance on the market of a new cutting mode with a lower coagulation effect has been proposed as an alternative to laser due to less injury to the tissue. OBJECTIVES: To study the clinical and functional consequences, as well as the side effects of this technique. Afterwards, we investigated whether the use of an electrosurgical knife with this technique is as effective and convenient as an ND-YAG-laser. PATIENTS AND METHODS: Between March 2005 and July 2007, included for study were 22 patients who had undergone 34 interventional bronchoscopy procedures with the VIO-300-D radiofrequency system, using a mode of the Endo-cut I program in conjunction with the reusable knife electrode. RESULTS: All of the patients treated (100%) presented improvements in their symptoms, in the tracheobronchial lumen diameter and in lung function, which were statistically significant. Symptom-free time was 157 ± 93 days. There was an overall decrease observed in mean obstruction (P<.001). Improvements in FVC (P=.01), Raw (P=.0016) and RV/TLC (P=.01) were significantly significant. Less than 50% of the patients needed a second intervention. These patients were compared retrospectively with a similar group of 22 patients treated with Nd-YAG laser. The follow-up analysis showed that only 18% (4/22) of the patients treated with this new technique presented fibrin, compared with 41% (9/22) of those treated with laser therapy (P<.001). CONCLUSION: The use of this technique is effective for the treatment of benign web-like tracheobronchial stenosis as all the patients showed clinical and functional improvement, and less than 50% required a second intervention. In comparison with laser therapy, an advantage of this technique is that less fibrin is produced, probably due to the reduced anti-coagulation effect.