[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model.

BACKGROUND: The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB. METHODS: Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points. RESULTS: 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001). CONCLUSION: Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.

Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma.

BACKGROUND: Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy. METHODS: In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under anti-IL-5 therapy) and timepoint 2 (T2, under anti-IL-5Rα therapy). RESULTS: Of 665 patients treated with anti-IL-5 antibodies, 70 were switched to anti-IL-5Rα and 60 were included in the analysis. Median treatment duration was 8 months [IQR 5; 15] for anti-IL-5 and 5 months [IQR 4; 6] for anti-IL-5Rα therapy. FEV1 was 61% of predicted at BL [IQR 41; 74], 61% [IQR 43; 79] at T1 and 68% [IQR 49; 87] at T2 (pT1-T2=0.011). ACT score was 10 [IQR 8; 13], 16 [IQR 10; 19] and 19 [IQR 14; 22], respectively (both p<0.001). The number of patients requiring OCS was reduced from 41 (BL) to 32 (T1) and 19 (T2) (both p<0.001). Ten patients discontinued anti-IL-5Rα therapy due to insufficient efficacy (n=7) and adverse events (n=3). CONCLUSION: Switching from anti-IL-5 to anti-IL-5Rα therapy in patients with inadequate response was associated with significantly improved FEV1, asthma control and OCS reduction.

Efficacy and Safety of the 9-mm Intrabronchial Valve in Patients with Advanced Emphysema.

BACKGROUND: Endoscopic valve therapy aims at lung volume reduction that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. The size of intrabronchial valves of the Spiration® Valve System (SVS) selected to achieve lobar occlusion may have an influence on treatment outcomes. METHODS: 49 severe emphysema patients (M/F: 24/25, age: 64 ± 7 years), with complete interlobar fissures on the side intended to be treated, underwent treatment with at least one 9-mm intrabronchial valve implantation at 3 centers and were followed up at 30, 90 and 180 days after intervention. Changes in pulmonary function tests (PFT), 6-min walk test (6MWT), modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive pulmonary disease assessment test scores as well as possible complications were recorded. RESULTS: Forced expiratory volume in 1 s (FEV1) improved significantly over the 6-month period of the study, and the proportion of patients achieving a minimal clinically important difference (MCID) for FEV1 was 46.4% at 6 months. Regarding the remaining PFT values, the changes were not statistically significant at 6 months, but when looking at the MCIDs, 44.4% of the patients achieved the MCID decrease for residual volume. The 6MWT distance also improved statistically significantly, and an MCID increase of ≥26 m was reached by 41.7% of the patients. Furthermore, there was a statistically significant improvement in the mMRC score. The incidence of pneumothoraxes requiring drainage was 26.5% while a valve dislocation rate of 24% was observed but only in the lower lobes. CONCLUSIONS: Endoscopic lung volume reduction with the 9-mm SVS valves was associated with statistically significant but modest improvement of FEV1, mMRC and 6MWT up to 6 months after intervention. These results were accompanied by an anticipated and acceptable risk profile. The relative increased incidence of device dislocation observed needs to be further elucidated.

Utility of Endobronchial Ultrasound in Assessment of Intrathoracic Lesions in Paediatric Patients.

INTRODUCTION: In adults, linear endobronchial ultrasound (EBUS) is the preferred modality to sample intrathoracic adenopathy and radial EBUS is a useful tool to biopsy peripheral pulmonary nodules. Utility in children is less well known. OBJECTIVES: The objective of this study was to review the EBUS experience of two specialist centres to better define the current role of EBUS in paediatric practice. METHODS: A retrospective record review of EBUS procedures undertaken in patients aged 0-17 years at the Royal Children's Hospital (Melbourne, Australia) and Thoraxklinik (Heidelberg, Germany) was performed. Data extracted included patient demographics, clinical presentation, bronchoscope (size and model), EBUS technique used, pathologic results, need for further invasive investigation, and complications. RESULTS: Between 2008 and 2017, ten EBUS procedures were performed (6 linear EBUS and 4 radial EBUS). No complications were reported. Linear EBUS was performed on subjects who were between 4 and 15 years old, with a 100% diagnostic yield. Radial EBUS was non-diagnostic in three cases of non-malignant disease. In one case, it was used successfully for imaging alone. CONCLUSION: Both linear and radial EBUS are safe and feasible in children. Diagnostic yield of linear EBUS was 100%. Radial EBUS did not demonstrate utility, likely reflecting the pathologies of underlying parenchymal masses in paediatric populations.

Disseminated Mycosis by Arthrocladium fulminans Jeopardizing a Patient with GATA2 Deficiency.

GATA2 deficiency is characterized by monocytopenia, deficiency of dendritic cells, and a variable degree of lymphocytopenia affecting B cells and NK cells, leading to an enhanced risk of mycobacterial, viral, and fungal infections. Here we present a patient with a heterozygous intronic GATA2 mutation who acquired a fatal disseminated mycosis due to the black yeast-like fungus Arthrocladium fulminans following an infection with Mycobacterium sherrisii. This case illustrates that in patients with severe uncommon infections, immunodeficiency syndromes must be ruled out.

Survival after Endoscopic Valve Therapy in Patients with Severe Emphysema.

BACKGROUND: Endoscopic valve therapy leads to an improvement of lung function, exercise tolerance, and quality of life in a selected cohort of patients with advanced emphysema. So far, only few data exist on the long-term outcome. OBJECTIVES: This analysis evaluated the impact of valve therapy on the survival of emphysema patients. METHODS: Survival rates of emphysema patients who underwent valve therapy were assessed according to their radiological outcome following valve placement. RESULTS: From 2005 to 2013, 449 emphysema patients (mean age 64 ± 7 years) underwent valve therapy and were followed for a mean time of 37.3 ± 21.3 months. A total of 128 patients (29%) developed complete lobar atelectasis, 34 out of these also experienced a pneumothorax; 50 patients (11%) developed pneumothorax without lobar atelectasis, and 261 patients (58%) target lobe volume reduction or no volume change. Patients with atelectasis showed significantly better baseline forced expiratory volume in 1 second (%), residual volume (L), total lung capacity (L), and transfer factor for carbon monoxide (%; all p < 0.05), but there was no significant difference in the BODE score (p = 0.195). Patients with valve-induced lobar atelectasis had a significant survival benefit compared to patients without atelectasis (p = 0.009; 5-year survival rate 65.3 vs. 43.9%). The advent of pneumothorax in 84 patients did not influence survival (p = 0.52). CONCLUSIONS: Lobar atelectasis following endoscopic valve therapy is associated with a survival benefit.

Quantitative CT detects changes in airway dimensions and air-trapping after bronchial thermoplasty for severe asthma.

OBJECTIVES: Bronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT). METHODS: Paired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval -950 to -856 in expiration to inspiration (RVC856-950) in a generation- and lobe-based approach, respectively. RESULTS: BT reduced WT for the combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p < 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVC856-950 decreased significantly after BT by 12.65% and 1.77% (p < 0.001), respectively. CONCLUSION: BT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure.

Endoscopic Valve Removal >180 Days since Implantation in Patients with Severe Emphysema.

BACKGROUND: Valve implantation provides a reversible effective therapy in a selected group of emphysema patients. Knowing predictors for successful therapy, the rate of treatment failure has decreased. Some patients, however, do not benefit, so that the valves may have to be removed. OBJECTIVES: To assess implant-related events, complications during valve removal, and clinical outcome after endoscopic procedure. METHODS: The data of 76 consecutive emphysema patients who underwent valve removal > 6 months since implantation were collected. RESULTS: Seventy-six patients (mean age 62 years, 54% male) underwent removal of all valves after a mean time of 624 days (193-3,043 days) since implantation. Granulation tissue was observed in 39.5% (30/76) and significant secretion in 34.2% (26/76). In 5.3% (4/76), valve removal was complicated requiring another bronchoscopy in 2 of them. In 5.3% (4/76) of the patients, one valve could not be removed and remained in situ. Bleeding requiring intervention occurred in 3.9% (3/76) during valve removal. Following bronchoscopy, there was a need for antibiotics in 34.2% (26/76), glucocorticosteroids in 1.3% (1/76), and both in 6.6% (5/76) due to productive cough or chronic obstructive pulmonary disease (COPD) exacerbation. Due to respiratory failure, invasive ventilation or noninvasive ventilation was necessary in 2.6% (2/76) and 6.6% (5/76), respectively, following procedure. No statistical significant change in lung function was observed following valve removal. CONCLUSIONS: Valve removal after > 6 months since implantation is feasible and associated with an acceptable safety profile. However, close monitoring of these patients with limited pulmonary reserve is recommended with particular attention to COPD exacerbations and respiratory failure.

Clinical and quantitative computed tomography predictors of response to endobronchial lung volume reduction therapy using coils.

Objectives: Bronchoscopic lung volume reduction using coils (LVRC) is a well-known treatment option for severe emphysema. The purpose of this study was to identify quantitative computed tomography (QCT) and clinical parameters associated with positive treatment outcome. Patients and methods: The CT scans, pulmonary function tests (PFT), and 6-minute walk test (6-MWT) data were collected from 72 patients with advanced emphysema prior to and at 3 months after LVRC treatment. The procedure involved placing 10 coils unilaterally. Various QCT parameters were derived using Apollo imaging software (VIDA). Independent predictors of clinically relevant outcome (Δ6-MWT ≥ 26 m, ΔFEV1 ≥ 12%, ΔRV ≥ 10%) were identified through stepwise linear regression analysis. Results: The response outcome for Δ6-MWT, for ΔFEV1 and for ΔRV was met by 55%, 32% and 42%, respectively. For Δ6-MWT ≥ 26 m a lower baseline 6-MWT (p = 0.0003) and a larger standard deviation (SD) of low attenuation cluster (LAC) sizes in peripheral regions of treated lung (p = 0.0037) were significantly associated with positive outcome. For ΔFEV1 ≥ 12%, lower baseline FEV1 (p = 0.02) and larger median LAC sizes in the central regions of treated lobe (p = 0.0018) were significant predictors of good response. For ΔRV ≥ 10% a greater baseline TLC (p = 0.0014) and a larger SD of LAC sizes in peripheral regions of treated lung (p = 0.007) tended to respond better. Conclusion: Patients with lower FEV1 and 6-MWT, with higher TLC and specific QCT characteristics responded more positively to LVRC treatment, suggesting a more targeted CT-based approach to patient selection could lead to greater efficacy in treatment response.

The Modern Art of Reading Computed Tomography Images of the Lungs: Quantitative CT.

Lung diseases are increasing in prevalence and overall burden worldwide. To stem the tide, more and more national and international guidelines are recommending the use of various diagnostic algorithms that are disease specific. There is growing consensus among the respiratory community that although patient histories and lung function testing are the minimum required for clinical examinations, these tests alone are not sufficient for disease characterization. Therefore, the use of computed tomography (CT) imaging is increasing used in clinical decision making for lung diseases. Lung diseases affect various components of lung, including the small airways, lung parenchyma, the interstitial space and the pulmonary vasculature. Quantitative CT (QCT) methods are emerging and are increasingly available using commercial software to quantify the underlying disease components, and a growing body of evidence suggests that QCT is an important tool in the clinical setting to help accurately and reproducibly detect where the disease is located in the lung, and to quantify the extent and overall severity for several lung diseases. Furthermore, this growing body of evidence has promoted the use of thoracic QCT to the point that it is now considered by many as an indispensable technology for longitudinal analysis and intervention trials. Many QCT imaging measurements are available to the respiratory physician, and the aim of this review is to introduce and describe pulmonary QCT imaging measurements and methodologies.

Coil therapy for patients with severe emphysema and bilateral incomplete fissures - effectiveness and complications after 1-year follow-up: a single-center experience.

BACKGROUND: Lung volume reduction coil (LVRC) treatment is established in daily endoscopic lung volume reduction routine. The aim of this study was to evaluate the safety and efficacy of LVRC treatment. PATIENTS AND METHODS: This was a retrospective analysis of 86 patients (male/female: 40/46, mean age: 64±7 years) with severe COPD and bilateral incomplete fissures. A total of 10 coils were unilaterally implanted in a single lobe, and 28 out of 86 patients were treated bilaterally. At 90-, 180-, and 365-day follow-up, changes in pulmonary function test (PFT), 6-minute walk test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications, were recorded. RESULTS: At 90 days, the forced expiratory volume in 1 second did improve (P<0.001), but the improvement was not sustained at the 180- and 365-day follow-up (baseline: 0.71±0.21 vs 0.77±0.23 vs 0.73±0.22 vs 0.70±0.18 L). Both vital capacity and residual volume improved significantly (P<0.001) at the 90- and 180-day follow-up, but the improvement was lost after 365 days. Total lung capacity decreased at the 90-day follow-up but returned to baseline values at the 180- and 365-day follow-up. 6MWT (P=0.01) and mMRC (P=0.007) also improved at 90 and 180 days (Δ6MWT of 31±54 and 20±60 m, respectively), but the improvement was also lost at the 365-day follow-up. No significant further improvement was evident at any point in the follow-up after the second procedure. A total of 4 out of 86 patients passed away due to complications. Significant complications in the first 3 months and then at 12 months included the following: severe hemoptysis in 4 (3.5%) and 4 (3.5%) patients, pneumonia requiring hospitalization in 32 (28.1%) and 9 (7.9%) patients and pneumothorax in 7 (6.1%) and 2 (1.7%) patients, respectively. Milder adverse events included self-limited hemoptysis, pneumonias, or COPD exacerbations treated orally. CONCLUSION: LVRC improved PFT, 6MWT and mMRC initially, but the improvement was lost after 365 days. Furthermore, we observed 4 deaths and significant severe complications, which need to be further elucidated.

Lung Volume Reduction with Vapor Ablation in the Presence of Incomplete Fissures: 12-Month Results from the STEP-UP Randomized Controlled Study.

BACKGROUND: Emphysema patients with collateral ventilation (CV) will not benefit from valve therapy, the most common endoscopic lung volume reduction procedure. A recent randomized controlled trial (STEP-UP) of the alternative bronchoscopic thermal vapor ablation (BTVA) included patients with (CV+) and without interlobar CV (CV-). OBJECTIVES: This analysis evaluated the efficacy and safety of the CV+ population following BTVA. METHOD: A post hoc fissure analysis of the baseline computed tomography of all treatment and control patients was performed with the VIDA Diagnostics Apollo software. A patient was considered to be CV+ if either of the treated upper lobes was adjacent to a fissure that was <90% complete. The primary endpoints, forced expiratory volume in 1 s (FEV1) and St. George's Respiratory Questionnaire (SGRQ-C), were calculated for these CV+ patients following BTVA and safety results summarized. RESULTS: 78% (35/45) of the patients in the treatment arm and 79% (19/24) of the patients in the control arm were found to be CV+. At 12 months, the FEV1 improvement of the treatment arm was 9.2%, as compared with a decrease of 5.4% in the control group, resulting in a mean between-group difference of 14.6% (p = 0.0137). The improvement in SGRQ-C of the treatment arm as compared to the control arm was 8.4 points (p = 0.0712). An increase in respiratory related serious adverse events was observed immediately following treatment, but most resolved with routine care. CONCLUSION: BTVA can achieve safe and clinically meaningful improvement in pulmonary function and quality of life in patients with CV. These randomized controlled trial subgroup results offer proof of a viable solution for CV+ patients.

Bronchoscopy in lung cancer: navigational modalities and their clinical use.

INTRODUCTION: More than 150,000 solitary pulmonary nodules are reported each year in the United States. As the popularity of low dose CT scan use for screening grows, these numbers are likely to increase substantially over the coming years. More than 10 million CT scans of the chest were performed in the United States alone in 2012, highlighting the potential for this clinical scenario. Detecting a nodule on either a chest radiograph or a CT scan frequently leads to a cascade of further investigations to establish a definite diagnosis. Thoracic surgery is frequently performed to obtain a tissue diagnosis in these cases, however, for what often turns out to be a benign abnormality. AREAS COVERED: During the last decade, several new technologies have been introduced to the field of bronchoscopy. As experience with these technologies has increased, the body of published literature has grown. Expert commentary: In this review, we assess the most important and interesting articles in the field. The value and the limitations of the various options will be discussed based on the actual evidence.

Endobronchial ultrasound: launch of an ERS structured training programme.

ERS launches structured EBUS training programme http://ow.ly/br5P302vhh3.

Endoscopic bronchial valve treatment: patient selection and special considerations.

As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility. The presence of high interlobar collateral ventilation will hinder successful treatment; therefore, endoscopic coil placement, polymeric lung volume reduction, or bronchoscopic thermal vapor ablation as well as lung volume reduction surgery can be used for treating patients with incomplete fissures. The effect of endoscopic lung volume reduction in patients with a homogeneous distribution of emphysema is still unclear and this subgroup should be treated only in clinical trials. Precise patient selection is necessary for interventions and to improve the outcome and reduce the risk and possible complications. Therefore, the patients should be discussed in a multidisciplinary approach prior to determining the most appropriate treatment for lung volume reduction.