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Lung cancer remains the deadliest cancer in the world, and lung cancer survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography screening can reduce mortality; however, annual screening is limited by low adherence in the United States of America and still not broadly implemented in Europe. As a result, less than 10% of lung cancers are detected through existing programs. Thus, there is a great need for additional screening tests, such as a blood test, that could be deployed in the primary care setting.

Die Digitalisierung wird die Medizin im Ganzen und die Pneumologie im Speziellen verändern. Digitalisierung sollte jedoch kein Selbstzweck sein. Ebenso wenig sollte und kann Digitalisierung die menschliche Komponente in der Medizin ersetzen. Patienten informieren sich jedoch zunehmend über Gesundheitsthemen im Internet, messen ihre Vitalwerte in der Häuslichkeit oder kommen bereits mit einer Diagnose „made by Dr. Google“. Ärzten kommt daher zunehmend eine Beraterfunktion zu, die einer der wichtigsten Aspekte einer menschlichen und empathischen Medizin ist. In diesem Sinne sollten Ärzte daher auch die digitale Transformation der Medizin proaktiv mitgestalten. Vor dem Hintergrund des Mottos des diesjährigen Kongresses werden wir in unserem Beitrag in die kürzere Vergangenheit blicken, aktuelle Entwicklungen aufnehmen und auch einen Blick in die Zukunft einer digitalen und empathischen Pneumologie wagen.

Hintergrund: Schweres Asthma stellt in Deutschland für betroffene Patient:innen und versorgende Einrichtungen ebenso wie für das Gesundheitssystem ein bleibendes Problem dar. Daher wurde das German Asthma Net (GAN) mit dem Ziel gegründet, die aktuelle Versorgungsrealität besser zu erfassen, das Krankheitsbild besser zu verstehen und die Behandlung zu optimieren. Fragestellung: Es erfolgt die Darstellung der Entwicklung des Registers Schweres Asthma des German Asthma Net e. V. seit Vereinsgründung. Material und Methode: Die Historie des Vereins mit Einblick in die Vereinsstruktur, Aufgabenverteilung sowie Aufbau und Entwicklung des Registers Schweres Asthma werden dargestellt. Ergebnisse: Seit Beginn der Vereinsgründung und der Etablierung des Registers Schweres Asthma ist ein kontinuierlicher Anstieg der Patientenzahl zu beobachten und damit verbunden eine gute Vernetzung wichtiger Wirkungskreise. Unter Mitarbeit von Registerzentren in Deutschland und Europa, Kooperationspartnern aufseiten von Fachgesellschaften und Sponsoring konnte das Register für schweres Asthma mit aktuell über 3700 Patient:innen aufgebaut werden. Patient:innen können sich über die Webseite eine geeignete Anlaufstelle für schweres Asthma suchen. Schlussfolgerung: Durch die enge Kooperation mit allen Beteiligten konnte das weltweit größte spezifische Register für schweres Asthma etabliert werden, mit dessen Hilfe wichtige Fragen zur Pathologie, Epidemiologie und Therapie der entsprechenden Patient:innen gestellt und beantwortet werden können. Das GAN stellt damit einen wichtigen Beitrag zur Optimierung der Versorgung dieser besonders betroffenen Patientengruppe dar.

Antibiotics, among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity. We hypothesized that early-life microbiome alterations would lead to increased susceptibility to allergy and asthma. To test this, mouse pups between postnatal days 5–9 were orally exposed to water (control) or to therapeutic doses of azithromycin or amoxicillin. Later in life, these mice were sensitized and challenged with a model allergen, house dust mite (HDM), or saline. Mice with early-life azithromycin exposure that were challenged with HDM had increased IgE and IL-13 production by CD4+T cells compared to unexposed mice; early-life amoxicillin exposure led to fewer abnormalities. To test that the microbiota contained the immunological cues to alter IgE and cytokine production after HDM challenge, germ-free mice were gavaged with fecal samples of the antibiotic-perturbed microbiota. Gavage of adult germ-free mice did not result in altered HDM responses, however, their offspring, which acquired the antibiotic-perturbed microbiota at birth showed elevated IgE levels and CD4+cytokines in response to HDM, and altered airway reactivity. These studies indicate that early-life microbiota composition can heighten allergen-driven Th2/Th17 immune pathways and airway responses in an age-dependent manner.

The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected not only ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT treatment, which increased the number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract.

Antibiotics, among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity. We hypothesized that early-life microbiome alterations would lead to increased susceptibility to allergy and asthma. To test this, mouse pups between postnatal days 5–9 were orally exposed to water (control) or to therapeutic doses of azithromycin or amoxicillin. Later in life, these mice were sensitized and challenged with a model allergen, house dust mite (HDM), or saline. Mice with early-life azithromycin exposure that were challenged with HDM had increased IgE and IL-13 production by CD4+T cells compared to unexposed mice; early-life amoxicillin exposure led to fewer abnormalities. To test that the microbiota contained the immunological cues to alter IgE and cytokine production after HDM challenge, germ-free mice were gavaged with fecal samples of the antibiotic-perturbed microbiota. Gavage of adult germ-free mice did not result in altered HDM responses, however, their offspring, which acquired the antibiotic-perturbed microbiota at birth showed elevated IgE levels and CD4+cytokines in response to HDM, and altered airway reactivity. These studies indicate that early-life microbiota composition can heighten allergen-driven Th2/Th17 immune pathways and airway responses in an age-dependent manner.

Background: Patients with obstructive sleep apnea (OSA) most commonly receive positive airway pressure therapy (PAP) as primary treatment, which is highly effective when used consistently. Little is known about the preferences for and relevance of attributes of OSA treatments, especially of non-PAP alternatives. The aim of this study was to evaluate treatment preferences and willingness to pay (WTP) among patients with and without previous experience of OSA therapies. Methods: A discrete choice experiment and a structured survey were applied to patients presenting for overnight polysomnography at a tertiary sleep center. Medical variables were obtained from hospital case records. Results: Over a period of 4 months, 241 subjects were enrolled and answered the questionnaire (61.8% with an existing diagnosis, 38.2% with a new diagnosis). The most preferred treatment among all patients was PAP therapy (51.1%), followed by mandibular advancement devices (18.1%), hypoglossal nerve stimulation (17.2%), and medication (13.7%). Approval for the different treatments varied by gender as well as by OSA therapy experience. The importance of attributes of OSA treatment varied too, with low rates of treatment-related side effects being equally important, independent of the preferred therapy. The most often stated monthly WTP for optimal sleep was € 50, with increasing age leading to lower WTP values. Conclusion: Preferences for OSA therapies vary among patients and patient subgroups. PAP therapy is the most preferred treatment, though non-PAP interventions receive high approval ratings too, particularly in treatment-naïve patients. The importance of treatment attributes varies as well, depending on the choice of preferred treatment.

Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition.

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Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19.

ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms.

Inhalation devices are the main method of delivering treatments to patients with chronic obstructive pulmonary disease (COPD). However, there are many devices available, which can lead to confusion and poor inhaler technique. To help doctors decide which device to give to their patients, they consider whether the patient would be happy with the device and whether they can use it correctly. This study pooled data from two large real-life studies to assess patient satisfaction with the Respimat®Soft Mist™ inhaler. Patients assessed their satisfaction and willingness to continue using the device at the end of the study period.

Eosinophils are predominantly known for their contribution to allergy. Here, we have examined the function and regulation of gastrointestinal eosinophils in the steady-state and during infection with Helicobacter pylori or Citrobacter rodentium. We find that eosinophils are recruited to sites of infection, directly encounter live bacteria, and activate a signature transcriptional program; this applies also to human gastrointestinal eosinophils in humanized mice. The genetic or anti–IL-5–mediated depletion of eosinophils results in improved control of the infection, increased inflammation, and more pronounced Th1 responses. Eosinophils control Th1 responses via the IFN-γ–dependent up-regulation of PD-L1. Furthermore, we find that the conditional loss of IFN-γR in eosinophils phenocopies the effects of eosinophil depletion. Eosinophils further possess bactericidal properties that require their degranulation and the deployment of extracellular traps. Our results highlight two novel functions of this elusive cell type and link it to gastrointestinal homeostasis and anti-bacterial defense.

Objective: To enlarge the donor pool for lung transplantation, an increasing number of extended criteria donor lungs are used. However, in more than 50% of multi-organ donors the lungs are not used. Ex vivo lung perfusion offers a unique possibility to evaluate and eventually recondition the injured donor lungs. The aim of our study was to assess the enlargement of the donor pool and the outcome with extended criteria donor lungs after ex vivo lung perfusion.Patients and Methods: Data were prospectively collected in our lung transplant database. We compared the results of lung transplants after ex vivo lung perfusion with those after conventional cold static preservation. In total, 11 extended criteria donor lungs processed with ex vivo lung perfusion and 41 cold static preservation lungs transplanted consecutively between May 2016 and May 2017 were evaluated. Normothermic ex vivo lung perfusion was performed according to the Toronto protocol for 4 h. Cold static preservation lungs were stored in low-potassium dextran solution.Results: Ex vivo lung perfusion lungs before procurement had significantly lower PaO2/FiO2(P/F) ratios and more X-ray abnormalities. There were no statistically significant differences for pre-donation ventilation time, smoking history, or sex. After reconditioning with ex vivo lung perfusion, 9 out of 11 processed lungs were considered suitable and successfully transplanted. The mean postoperative ventilation time and in-hospital stay were not significantly different in ex vivo lung perfusion and cold static preservation recipients.Conclusion: Ex vivo lung perfusion can safely be used in the evaluation of lungs initially considered not suitable for transplantation. The primary outcome was not negatively affected and normothermic ex vivo lung perfusion is a useful tool to increase the usage of potentially transplantable lungs.

The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice(IP) single-arm, open-label extension substudy.

Asthma is increasingly recognized as heterogeneous, characterized by different endotypes, with obesity not only a distinct phenotype but a risk factor for severe asthma.

Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS), nor been compared to effectiveness of continuing with HOCS alone.

Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as possible goal even in severe asthma.

Right ventricular (RV) function has not been systematically assessed in sarcoidosis. The aim of this study was to assess the prevalence and associates of RV dysfunction in sarcoidosis using global longitudinal peak systolic strain (GLS). Furthermore, whether RV dysfunction was associated with clinical outcomes was investigated.

Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

The management of care of chronic obstructive pulmonary disease improved over the last years but is still very complex. Both over- and underdiagnosis are often reported and misclassification of disease severity is common. Differentiating between chronic obstructive pulmonary disease, asthma and asthma-chronic obstructive pulmonary disease overlap syndrome remains difficult. Much is known about the effectiveness of treatment approaches in chronic obstructive pulmonary disease, but patients are often not treated according to the guidelines, and we need more evidence on effectiveness in phenotypes of chronic obstructive pulmonary disease. Care coordination is of great importance and can help to further improve care for chronic obstructive pulmonary disease patients. Pulmonary rehabilitation and self-management are considered important aspects of chronic obstructive pulmonary disease care. In our opinion, there is a major role for eHealth to improve coordination of care of chronic obstructive pulmonary disease.

In den letzten Jahren ist eine deutliche Entwicklung in der Medizin hin zu personalisierten Therapieansätzen zu beobachten. Auch bei der Behandlung des Asthma bronchiale sind in den letzten Jahren erhebliche Fortschritte in unserem Verständnis der Erkrankung erzielt worden. Dieses scheint nun auch in spezifische Therapieansätze zu resultieren, die nicht für alle Patienten sondern nur für eine spezifische Gruppe eingesetzt werden. Dazu gehören neben dem bereits zugelassenen anti-IgE auch neue Antikörper so wie anti-IL-5 und anti-IL-13. Für welche Patientengruppen diese am besten eingesetzt werden können ist zur Zeit Stand der Forschung. Zitierweise:Taube C. Bronchial Asthma: is personalized therapy on the horizon? Allergo J Int 2014; 23:246–51 DOI: 10.1007/s40629-014-0028-y

Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine.

Omalizumab is approved for the treatment of severe allergic asthma.

Naturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cAMP synthesis prevents gp120-mediated Treg activation. Employing a xenogeneic graft versus host disease model that has been shown to be applicable for the functional analysis of human Tregs in vivo, we further show that a single dose of gp120 is sufficient to prevent lethal graft versus host disease and that the tolerizing effect of gp120 is strictly dependent on the presence of human Tregs and their up-regulation of cAMP upon gp120-mediated activation. Our findings demonstrate that stimulation via the CD4 receptor represents a T-cell receptor–independent Treg activating pathway with potential to induce immunologic tolerance in vivo.

Naturally occurring CD4+CD25+regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cAMP synthesis prevents gp120-mediated Treg activation. Employing a xenogeneic graft versus host disease model that has been shown to be applicable for the functional analysis of human Tregs in vivo, we further show that a single dose of gp120 is sufficient to prevent lethal graft versus host disease and that the tolerizing effect of gp120 is strictly dependent on the presence of human Tregs and their up-regulation of cAMP upon gp120-mediated activation. Our findings demonstrate that stimulation via the CD4 receptor represents a T-cell receptor–independent Treg activating pathway with potential to induce immunologic tolerance in vivo.

Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell–derived cytokines TNF-α and IL-1β play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell–derived IL-1β. We have previously shown that TLR7 ligation enhances transcutaneous immunization evoked by topical application of vaccine antigens to the skin, a procedure that directly targets skin-resident antigen-presenting cells. Consequently, we now demonstrate here that the capacity to mount a peptide-specific cytotoxic T-lymphocyte response following transcutaneous immunization using imiquimod as adjuvant is severely impaired in mast-cell–deficient mice. Thus, these findings demonstrate the potent versability of alternatively activated mast cells at the interface of innate and adaptive immunity.