Silent Hypoxia in COVID-19: A Case Series.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global crisis challenging the worldwide healthcare systems. Many patients present with a mismatch of profound hypoxemia and few signs of respiratory distress (i.e., silent hypoxemia). This particular clinical presentation is often cited, but data are limited. MAIN BODY: We describe dyspnea sensation as assessed by using the BORG scale in pulmonary patients admitted to the emergency room during a 4-week period and transferred to the respiratory department of Siloah Hospital, Hannover, Germany. From October 1 to November 1, 2020, 82 patients with hypoxemia defined as oxygen demand to achieve an oxygen saturation (SpO2) ≥92% were included. In 45/82 (55%) patients, SARS-CoV-2 was detected by PCR on admission. Among non-COVID patients, exacerbation of COPD was the main diagnosis (15/37, 41%). All subjects rated their perceived dyspnea using the modified Borg CR10 scale. Patients in the non-COVID group suffered from more dyspnea on the modified Borg CR10 scale (median 1, IQR: 0-2 vs. median 5, IQR: 3-6, p < 0.001). In multivariate analysis, "silent hypoxemia" as defined by the dyspnea Borg CR10 scale ≥5 was independently associated with COVID-19 and presence of severe hypocapnia with an odds ratio of 0.221 (95% confidence interval 0.054, 0.907, p 0.036). CONCLUSION: Among pulmonary patients with acute hypoxemia defined as oxygen demand, patients suffering from COVID-19 experience less dyspnea compared to non-COVID patients. "Silent" hypoxemia was more common in COVID-19 patients.

A Before-and-After Study of Evidence-Based Recommendations for On-Call Bronchoscopy.

BACKGROUND: Bronchoscopy is widely used and regarded as standard of care in most intensive care units (ICUs). Data concerning recommendations for on-call bronchoscopy are lacking. OBJECTIVES: Evaluation of recommendations, complications, and outcome of on-call bronchoscopies. METHOD: A retrospective single-centre analysis was conducted in a large university hospital. All on-call bronchoscopies performed outside normal working hours in the year before (period 1) and after (period 2) establishing a catalogue of recommendations for indications of on-call bronchoscopy on November 1, 2016, were included. RESULTS: Overall, 924 bronchoscopies in 538 patients were analysed. A relative reduction of 83.6% from 794 bronchoscopies in 432 patients (1.84 per patient) during period 1 to 130 in 107 patients (1.21 per patient) during period 2 was observed. Most bronchoscopies (812/924, 87.9%) were performed in ICUs, and 416 patients (77.3%) were intubated. Bronchoscopies for excessive secretions decreased significantly during period 2. Fifty-three of 130 bronchoscopies (40.8%) fulfilled the specified recommendations during period 2, in comparison with 16.8% in period 1 (p < 0.001). Complications were recorded in 58 of 924 procedures (6.3%) and were more frequent in period 2, especially moderate bleeding. In-hospital mortality of patients undergoing on-call bronchoscopy did not differ between periods and was 28.7 and 30.2% in periods 1 and 2, respectively. CONCLUSION: The introduction of recommendations for on-call bronchoscopy led to a significant decline of on-call bronchoscopies without negatively affecting outcome. More evidence is needed in on-call bronchoscopy, especially for ICU patients with intrinsic higher complication rates.

C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia.

Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle. Purified Glc-DAG triggered Mincle reporter cell activation and stimulated inflammatory cytokine release by human alveolar macrophages and alveolar macrophages from WT but not Mincle KO mice. Mincle deficiency led to increased bacterial loads and decreased survival together with strongly dysregulated cytokine responses in mice challenged with focal pneumonia inducing S. pneumoniae, all of which was normalized in Mincle KO mice reconstituted with a WT hematopoietic system. In conclusion, the Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.

Therapeutic approach to respiratory infections in lung transplantation.

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation.

Lung transplantation after endoscopic lung volume reduction.

BACKGROUND: Endoscopic lung volume reduction (ELVR) has become an established treatment option in selected patients with end-stage lung emphysema. ELVR, however, does not always prevent disease progression, and patients may inevitably be considered for lung transplantation. OBJECTIVES: Currently, limited data exist regarding the impact of preceding ELVR on lung transplantation outcomes. METHODS: A retrospective, single-center analysis of lung transplantation (LTx) waiting list candidates, who had previously undergone ELVR for emphysema between 2010 and 2014, was performed. Outcomes were compared to matched (1:2) controls who underwent LTx for emphysema without previous ELVR. The 12-month survival after LTx represented the primary end point. RESULTS: In total 23/693 (3%) patients listed for LTx between January 2010 and May 2014 had undergone ELVR, of whom 20/23 (87%) proceeded to LTx (ELVR group). Forty matched non-ELVR emphysema patients acted as controls. Bronchiectasis on CT prior to LTx was more evident in ELVR patients [11/20 (55%) vs. 12/40 (30%); p = 0.04] as well as airway colonization after LTx [10/20 (50%) vs. 6/40 (15%); p = 0.004]. Among ELVR patients, the most prevalent colonizing organism was Stenotrophomonas maltophilia (4/10 patients, 40%). No significant differences were observed in LTx waiting list time, duration of LTx procedure, ventilatory support, ICU stay after LTx or time to hospital discharge. One ELVR patient (5%) died 189 days after LTx from pneumonia, compared to 1 non-ELVR patient (3%) who died after 269 days (p = 0.61). CONCLUSIONS: Previous ELVR treatment was not associated with differing outcomes following LTx. Increased bacterial colonization rates were evident and warrant further investigation.

Therapeutic plasma exchange as rescue therapy in severe sepsis and septic shock: retrospective observational single-centre study of 23 patients.

BACKGROUND: Several case series and small randomized controlled trials suggest that therapeutic plasma exchange (TPE) improves coagulation, hemodynamics and possibly survival in severe sepsis. However, the exact role of TPE in modern sepsis therapy remains unclear. METHODS: We performed a retrospective observational single-centre study on the use of TPE as rescue therapy in 23 consecutive patients with severe sepsis or septic shock from 2005 to 2012. Main surrogate markers of multiple organ failure (MOF) before, during and after TPE as well as survival rates are reported. RESULTS: At baseline, mean SOFA score was 13 (standard deviation [SD] 4) and median number of failed organ-systems was 5 (interquartile range [IQR] 4-5). TPEs were performed 3 days (IQR 2-10) after symptom onset and 1 day (IQR 0-8) after ICU admission. The median total exchange volume was 3750 ml (IQR 2500-6000), which corresponded to a mean of 1.5 times (SD 0.9) the individual plasma volume. Fresh frozen plasma was used in all but one treatments as replacement fluid. Net fluid balance decreased significantly within 12 hrs following the first TPE procedure by a median of 720 mL (p = 0.002), irrespective of outcome. Reductions of norepinephrine dose and improvement in cardiac index were observed in individual survivors, but this was not significant for the overall cohort (p = 0.574). Platelet counts decreased irrespective of outcome between days 0 and 2 (p < 0.003), and increased thereafter in many survivors. There was a non-significant trend towards younger age and higher procalcitonin levels among survivors. Nine out of 23 TPE treated patients (39%) survived until ICU discharge (among them 3 patients with baseline SOFA scores of 15, 17, and 20). CONCLUSIONS: Our data suggest that some patients with severe sepsis and septic shock may experience hemodynamic stabilisation by early TPE therapy.

Outcomes and Functional Deterioration in Hospital Admissions with Acute Hypoxemia.

BACKGROUND: Many hospitalized patients decline in functional status after discharge, but functional decline in emergency admissions with hypoxemia is unknown. The primary aim of this study was to study functional outcomes as a clinical endpoint in a cohort of patients with acute hypoxemia. METHODS: A multicenter prospective observational study was conducted in patients with new-onset hypoxemia emergently admitted to two respiratory departments at a university hospital and an academic teaching hospital. Using the WHO scale, the patients' functional status 4 weeks before admission and at hospital discharge was assessed. The type and duration of oxygen therapy, hospital length of stay and survival and risk of hypercapnic failure were recorded. RESULTS: A total of 151 patients with a median age of 74 were included. Two-thirds declined in functional status by at least one grade at discharge. A good functional status (OR 4.849 (95% CI 2.209-10.647)) and progressive cancer (OR 6.079 (1.197-30.881)) were more associated with functional decline. Most patients were treated with conventional oxygen therapy (n = 95, 62%). The rates of in-hospital mortality and need for intubation were both 8%. CONCLUSIONS: Patients with acute hypoxemia in the emergency room have a poorer functional status after hospital discharge. This decline may be of multifactorial origin.

Effect of a biomimetic pathogen adsorbing device on inflammatory biomarkers in COVID-19 patients.

INTRODUCTION: The Seraph 100 Microbind Affinity blood filter eliminate bacteria, viruses, fungi and toxins from blood stream. METHODS: This is a prospective multicenter observational biomarker trial in PCR-positive SARS-CoV-2 patients with acute respiratory failure. Biomarkers were sequentially tested at three time points. RESULTS: Forty-two patients with SARS-CoV-2 detected by PCR with acute respiratory failure were included. When receiving hemoperfusion treatment, 27 (64%) patients were on mechanical ventilation, 41 (98%) patients were treated in the ICU. The 3-month survival was 52%. After one hemoperfusion treatment cycle, D-dimer (p = 0.014), hemoglobin (p = 0.003) and LDH (p = 0.001) concentrations were significantly reduced 4 days after treatment. From the multiplex assay IL-1b, CXCL8/ IL-8, IL-10, IL-13, IL-15, CCL11/Eotaxin, G-CSF, and CXCL10/IP-10 were significantly reduced 1 h after treatment, however not 4 days later. CONCLUSION: Hemoperfusion with Seraph 100 Microbind Affinity Filter in patients with severe COVID-19 can transiently reduce several inflammatory biomarkers in the blood.

Antihypertensives suppress the emergence of fluoroquinolone-resistant mutants in pneumococci: an in vitro study.

BACKGROUND: The antihypertensives reserpine and verapamil are also inhibitors of pneumococcal efflux pumps. We addressed the following questions: (i) Do verapamil and reserpine influence the mutation ratio of pneumococci in the presence of ciprofloxacin? (ii) At which concentrations does this occur? (iii) Is this limited to isolates with efflux phenotype? METHODS: 14 clinical isolates, nested in 6 genetically similar clusters, were used, 7 strains with efflux and 7 without. The mutation ratio in the presence of ciprofloxacin (3 × MIC) and increasing concentrations of reserpine and verapamil was determined and the quinolone-resistance determining regions (QRDR) of selected mutants were sequenced. Analysis of the efficacy was performed using a mixed linear model, supported by descriptive statistics. RESULTS: Reserpine and verapamil reduced the mutation ratio of QRDR in the presence of ciprofloxacin with the required concentration for a reduction ≥ 50% of 1mg/l for reserpine and 50mg/l for verapamil. The mutation prevention effect is not limited to, but is more pronounced in efflux positive phenotypes. CONCLUSION: Reserpine and verapamil can prevent the selection of ciprofloxacin resistant isolates by reduction of the mutation ratio, particularly in strain with an efflux phenotype. However, the required concentrations are too toxic for clinical use.

The influence of clinical course after lung transplantation on rehabilitation success.

Pulmonary rehabilitation (PR) is a cornerstone of treatment following lung transplantation (LTx). The aim of this study was to observe the influence of a prolonged postsurgical clinical course on success of a 3-week inpatient PR. LTx recipients were divided according to their clinical course defined by their individual length of stay (LOS) in the transplant center (cohort 1: LOS >; cohort 2: ≤42 days). Peak work rate (PWR), maximum oxygen uptake (VO(2max) ), 6-min walk distance (6-MWD), vital capacity (VC), forced expiratory volume in one second (FEV1), physical activity of daily life (ADL), and health-related quality of life (HRQoL) measured using Short Form 36 questionnaire (SF36) were assessed at beginning and completion of PR. A total of 138 patients were included (LOS >42 days: 30; LOS ≤42 days: 108). At completion, physical functioning (VC, FEV1, PWR, VO(2max) , 6-MWD, ADL), and HRQoL (all SF36 domains) improved in each cohort (P < 0.05). No differences were found in between both cohorts in VC, FEV1, and ADL (n.s.), but in PWR, 6-MWD, and the SF36 domain 'physical functioning' (P < 0.05). A 3-week inpatient PR improves physical functioning despite prolonged hospitalization. HRQoL is close to normal. (ClinicalTrials.gov. identifier: NCT00759538).

Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation.

RATIONALE: The use of extracorporeal membrane oxygenation (ECMO) in patients who are awake and spontaneously breathing may represent a novel bridging strategy toward lung transplantation (LuTx). OBJECTIVES: To evaluate the outcomes of patients treated with the "awake ECMO" concept as bridge to transplantation. METHODS: We performed a retrospective, single-center, intention-to-treat analysis of consecutive LuTx candidates with terminal respiratory or cardiopulmonary failure receiving awake ECMO support. The outcomes were compared with a historical control group of patients treated with conventional mechanical ventilation (MV group) as bridge to transplant. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (58% female; median age, 44 yr; range, 23-62) were included in the awake ECMO group and 34 patients (59% female; median age, 36 yr; range, 18-59) in the MV group. The duration of ECMO support or MV, respectively, was comparable in both groups (awake ECMO: median, 9 d; range, 1-45. MV: median, 15 d; range, 1-71; P = 0.25). Six (23%) of 26 patients in the awake ECMO group and 10 (29%) of 34 patients in the MV group died before a donor organ was available (P = 0.20). Survival at 6 months after LuTx was 80% in the awake ECMO group versus 50% in the MV group (P = 0.02). Patients in the awake ECMO group required shorter postoperative MV (P = 0.04) and showed a trend toward a shorter postoperative hospital stay (P = 0.06). CONCLUSIONS: ECMO support in patients who are awake and nonintubated represents a promising bridging strategy, which should be further evaluated to determine its role in patients with end-stage lung disease awaiting LuTx.

Management and outcome of obstructive airway complications after lung transplantation - a 12-year retrospective cohort study.

BACKGROUND: Obstructive airway complications (OACs) represent a significant problem after lung transplantation (LTx). Bilateral OACs after double lung transplantation are infrequently reported. OBJECTIVES: The aim of this study was to investigate management and outcome of OAC. DESIGN: Retrospective single-center cohort study. METHODS: Adult patients with bilateral LTx performed between 2010 and 2021 were included. Patients with follow-ups of less than 3 months and after heart-lung transplantation were excluded. OAC was defined either as the need for stenting, surgical revision, or balloon dilatation. Outcome parameters included graft survival, graft function, quality of life, and management. RESULTS: During the study period, 1,170 patients were included. Hundred thirty-five (11.5%) patients developed OAC. Forty-six (4.4%) patients had significant bilateral OAC. Thirty-seven (80%) bilateral OAC patients were treated by stent insertion; in 34 patients, biodegradable stents were used. The median number of bronchoscopies in bilateral OAC was 26 during the first postoperative year compared with nine in controls (p < 0.001). Fourteen OAC patients (n = 10 bilateral) underwent surgical revision including six re-do transplantations. Graft loss occurred significantly more frequently in patients with bilateral OAC with a graft survival of 63% and 50% in these after 3 and 5 years compared with 83% and 73% in controls without OAC (p < 0.001). Baseline forced expiratory volume in 1 s (FEV1) in patients with bilateral OAC was median 58% predicted in comparison with 90% in controls (p < 0.001). Quality of life was significantly reduced. CONCLUSION: Bilateral OACs impose a high burden of disease on patients after lung transplantation and were associated with early and late graft loss. Affected patients' OAC demonstrated reduced graft function and impaired quality of life. Most OACs were managed by bronchoscopy preferably by non-permanent stenting. Surgery including re-do transplantation was used in selected cases.

Assessing treatment outcomes in CLAD: The Hannover-extracorporeal photopheresis model.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treatment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course. METHODS: Retrospective analysis of patients completing ≥3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were compared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation. RESULTS: Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photopheresis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation. CONCLUSIONS: Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treatment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible.

The lung transplant patient in the ICU.

PURPOSE OF REVIEW: Lung transplantation (LTx) has become established as a standard intervention for patients suffering from end-stage lung disease. Transplant recipients are, however, predisposed to numerous unique complications arising from the surgery, transplant immunology and the lifelong medication. Clinicians working in intensive care are increasingly likely to be exposed to these patients and it is therefore important to have a working knowledge of the common complications. RECENT FINDINGS: Common complications encountered following LTx include primary graft dysfunction (PGD), airway complications, acute rejection, chronic lung allograft dysfunction (CLAD), thrombotic microangiopathy (TMA) and infection, all of which impact significantly on long-term survival. PGD arises in the first weeks following transplantation. Acute rejection, airway complications and TMA represent the main complications in the first posttransplantation year. CLAD usually occurs later, but continues to represent the main obstacle to long-term survival. Infection poses significant risk at all stages following transplantation and a full spectrum of bacterial, fungal and viral pathogens has been implicated. SUMMARY: This review highlights the most important complications after LTx and gives an update on diagnostic algorithms and treatment challenges for patients following LTx.

Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes.

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Use of telehealth technology for home spirometry after lung transplantation: a randomized controlled trial.

CONTEXT: Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry. OBJECTIVE: To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients. DESIGN: Single-center prospective randomized controlled trial. Intervention-Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages. MAIN OUTCOME MEASURES: Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point. RESULTS: Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P = .73). Median time to first consultation (P = .60) and frequency of consultation (P = .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0-4.0) than in the home spirometry alone group (4.0; range, 2.0-6.0; P = .04). CONCLUSION: Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

Three Patients With Acute Pulmonary Damage Following the Use of E-Cigarettes-A Case Series.

BACKGROUND: The use of e-cigarettes is on the rise around the world. Many case reports of acute lung injury due to e-cigarette use have been published in recent months in the USA, but no comparable cases have emerged in Germany up to the present report. The use of e-cigarettes has risen very rapidly in the USA in recent years, simultaneously with the legalization of marijuana sale in many American states. Most of the cases described there involved the use, not only of nicotine, but of tetrahydrocannabinol (THC, the psychoactive ingredient in marijuana) as well, though some of the patients had indeed not used additives (e.g. THC). METHODS: We report three cases in Germany of acute pulmonary illness that we consider to have been caused by the use of e-cigarettes. RESULTS: All three patients were hospitalized for acute shortness of breath. Two displayed partial respiratory insufficiency and bilateral pulmonary infiltrates. All three stated that they had used ordinary, commercially available e-cigarettes every day for at least the past three months. In the first patient, a 48-year-old man, the complete blood count and bronchial lavage findings indicated eosinophilic inflammation. The second patient, a 22-year-old man, developed multiple episodes of hemoptysis, with computed tomography (CT) showing diffuse alveolar bleeding; his complete blood count also revealed eosinophilic inflammation. The third patient, a 34-year-old man, displayed acute ground-glass lung opacities as well as fibrosing changes on CT corresponding to pulmonary sarcoidosis. All three recovered on high-dose systemic corticosteroid treatment and were discharged from the hospital in 2 to 12 days. CONCLUSION: In the first two cases, acute pulmonary injury was very likely due to e-cigarette consumption, as all other possible causes were ruled out. A possible link to e-cigarette use was present in the third case. We thus describe the first three suspected cases of acute lung disease due to e-cigarette use in Germany. These patients do not share any common, typical clinical picture; rather, their symptoms represent different components of the wide spectrum of interstitial lung disease. A uniform national registry should be established to improve our understanding of the adverse effects of e-cigarettes and the resulting acute and chronic changes in the lungs.

T helper type 2 differentiation is associated with induction of antibacterial defense mechanisms in blood lymphocytes of patients with sarcoidosis.

Whereas sarcoidosis is characterized by an excessive inflammatory immune response mainly at the pulmonary site, circulating T lymphocytes poorly respond to antigen challenge. It has been suggested, that the extensive local inflammation might be triggered by bacterial pathogens. Recently, it has been shown that this paradoxically immunological situation likely results from a disequilibrium between effector and regulatory T lymphocytes (T(reg)). Here, we apply a DNA microarray approach in order to analyze circulating T cells for specific dysregulatory events, which should provide detailed insights in the impairment of cell-mediated immunity. Gene expression profiles were performed from peripheral blood T lymphocytes of untreated patients with pulmonary sarcoidosis (stage I) (n = 3) and a control group consisting of healthy donors (n = 3). Circulating T lymphocytes in sarcoidosis exhibit a specific gene expression pattern of molecules that are primarily involved in immune responses and lymphocyte signalling. Compared to controls patients with sarcoidosis display also alterations in gene expression of molecules with bacteriolytic and chemotactic function. Among others, array analysis resulted in increased transcript levels of Th2 immune response, whereas genes coding for molecules involved in Th1 differentiation are down-regulated. Furthermore, genes encoding proteins representing primordial antimicrobial peptides which may mobilise immunocompetent T cells and other inflammatory cells are up-regulated. This observation supports recent reports suggesting that bacterial antigens play a role in the pathogenesis of sarcoidosis. However, the results of our study indicate an unbalanced immune response towards Th2 in the peripheral blood of patients with sarcoidosis.