[Is JAK inhibition an option in the treatment of interstitial lung disease in rheumatoid arthritis?] / Ist JAK-Hemmung eine Option in der Behandlung der interstitiellen Lungenerkrankung bei einer rheumatoiden Arthritis?

A 69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and a lymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a 33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD.

Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

OBJECTIVES: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. METHODS: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. RESULTS: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. CONCLUSION: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Diagnosing lung involvement in inflammatory rheumatic diseases-Where do we currently stand?

Lung involvement is the most common and serious organ manifestation in patients with inflammatory rheumatic disease (IRD). The type of pulmonary involvement can differ, but the most frequent is interstitial lung disease (ILD). The clinical manifestations of IRD-ILD and severity can vary from subclinical abnormality to dyspnea, respiratory failure, and death. Consequently, early detection is of significant importance. Pulmonary function test (PFT) including diffusing capacity of the lungs for carbon monoxide (DLCO), and forced vital capacity (FVC) as well as high-resolution computed tomography (HRCT) are the standard tools for screening and monitoring of ILD in IRD-patients. Especially, the diagnostic accuracy of HRCT is considered to be high. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) allow both morphological and functional assessment of the lungs. In addition, biomarkers (e.g., KL-6, CCL2, or MUC5B) are being currently evaluated for the detection and prognostic assessment of ILD. Despite the accuracy of HRCT, invasive diagnostic methods such as bronchoalveolar lavage (BAL) and lung biopsy are still important in clinical practice. However, their therapeutic and prognostic relevance remains unclear. The aim of this review is to give an overview of the individual methods and to present their respective advantages and disadvantages in detecting and monitoring ILD in IRD-patients in the clinical routine.

Assessing the diagnostic value of a potential screening tool for detecting early interstitial lung disease at the onset of inflammatory rheumatic diseases.

BACKGROUND: Interstitial lung disease (ILD) is a severe pulmonary complication in inflammatory rheumatic diseases (IRD) and associated with significantly increased morbidity and mortality. That is why ILD screening at a very early stage, at the onset of IRD, is essential. The objective of the present study was to evaluate the diagnostic value and utility of a stepwise approach as a potential ILD screening tool in patients with newly diagnosed IRD. METHODS: Consecutively, 167 IRD patients were enrolled. To homogenize the study cohort, an age and gender matching was performed. The case-control study included 126 patients with new onset of IRD (mainly connective tissue diseases [CTD], small vessel vasculitis, and myositis). We applied a stepwise screening algorithm in which all patients underwent pulmonary function testing (PFT) and/or additional chest radiography. If there was at least one abnormal finding, pulmonary high-resolution computed tomography (HRCT) was subsequently performed. RESULTS: With our stepwise diagnostic approach, we identified 63 IRD patients with ILD (ILD group) and 63 IRD patients without ILD (non-ILD group). A reduced diffusing capacity for carbon monoxide (DLCO) < 80% showed a sensitivity of 83.6% and a specificity of 45.8% compared to chest X-ray with 64.2% and 73.6%, respectively, in detecting ILD. The combination of reduced DLCO and chest X-ray revealed a sensitivity of 95.2% and a specificity of 38.7%. The highest sensitivity (95.2%) and specificity (77.4%) were observed for the combination of reduced DLCO, chest X-ray, and pulmonary HRCT. The most common pulmonary abnormalities on HRCT were ground-glass opacities (GGO; 36.5%), followed by non-specific interstitial pneumonia (NSIP; 31.8%) and usual interstitial pneumonia (UIP; 9.5%). CONCLUSIONS: The combination of reduced DLCO (< 80%), chest X-ray, and pulmonary HRCT yielded the highest sensitivity and specificity in detecting ILD at the onset of IRD. Therefore, this stepwise approach could be a new screening algorithm to identify IRD patients with pulmonary involvement already at the time of the initial IRD diagnosis.

Current role of emergency ultrasound of the chest.

OBJECTIVE: Chest sonography has gained clinical significance in the diagnosis of various pulmonary, pleural, cardiac, and mediastinal emergency conditions. Therefore, the current role of emergency ultrasound are assessed. DATA SOURCE: A systematic literature search of MEDLINE database was performed to identify all studies dealing with transthoracic sonography/chest ultrasound in combination with pulmonary embolism, pneumothorax, pneumonia, pleural effusion, pulmonary edema, and lung contusion. The relevant sonographic studies between 1988 and 2010 were evaluated. CONCLUSIONS: The noninvasive ultrasound-based diagnosis is relatively portable permitting the technique to be performed at any time, in any place, and on any patient, an ideal method for emergency conditions. Sonography allows immediate diagnosis of pulmonary embolism, pneumothorax, pneumonia, pleural effusion as well as rib fracture, and it provides a basis for further diagnostic- and treatment-related decisions. The key sonographic features associated with these most common emergency chest diseases are illustrated herein.

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases.

BACKGROUND: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. MATERIALS AND METHODS: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. RESULTS: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. CONCLUSION: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Transthoracic sonography in comparison to multislice computed tomography in detection of peripheral pulmonary embolism.

The aim of the study was to compare transthoracic sonography (TS) with multislice computed tomography (MSCT) in the detection of peripheral pulmonary embolism (PE). In addition, the study verified peripheral parenchymal findings visualized by TS and MSCT. A total of 33 patients (16 females, 17 males; mean age = 65.4 years) with symptoms of suspected PE were enrolled in the study. TS and MSCT were undertaken within 24 h of the beginning of clinical PE signs. Ten patients suffered from PE as visualized by MSCT. The sensitivity of TS for detecting PE was 70.0% and the specificity was 69.6%. Preferentially, PE and peripheral parenchymal findings were situated in the lower lobes. Oligemia was the main parenchymal alteration detected by MSCT. TS demonstrated that wedge-shaped consolidations were frequently associated with PE. In addition, localized pleural effusion was a typical finding in the presence of PE for both TS and MSCT. TS had moderate sensitivity and specificity compared with MSCT. Furthermore, the study revealed that PE is often associated with peripheral parenchymal changes, both of which are detectable by TS and MSCT. In case of contraindication with MSCT, TS is a potential technique for diagnosing PE-related parenchymal findings and can serve as an alternative method in the diagnosis of PE. However, a negative result with TS does not rule out a PE.

Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma.

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years. Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6-17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK. A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives. Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.

Interferon-α for Induction and Maintenance of Remission in Eosinophilic Granulomatosis with Polyangiitis: A Single-center Retrospective Observational Cohort Study.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by frequent relapses following induction therapy. Interferon-α (IFN-α) can reverse the underlying Th2-driven immune response and has successfully induced remission in previous reports. We undertook this study to investigate its efficacy and safety in patients with EGPA. METHODS: We conducted a retrospective monocentric cohort study including 30 patients (16 women) with active EGPA under IFN-α treatment. Primary endpoints were remission induction, occurrence of relapses, prednisolone (PSL) dosage at time of remission, and adverse events. Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0. Pulmonary function tests were recorded at baseline and at time of remission. Health-related quality of life was analyzed by questionnaire at baseline and following 12 months of treatment. RESULTS: At baseline, the median BVAS was 6 (interquartile range 4-13.5) and remission or partial response was achieved in 25/30 patients. After initiation of IFN-α treatment, the median PSL dosages could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission. Following remission, 17 relapses (5 major) in 16 patients were observed. Pulmonary function tests improved and the time of hospitalization decreased. Adverse events at initiation of treatment were common, but mostly transient. Severe adverse events occurred during treatment in 4 patients (autoimmune hepatitis, n = 1; drug-induced neuropathy, n = 3). CONCLUSION: IFN-α treatment results in high rate of remission and maintenance in EGPA with significant reduction in oral corticosteroids, although reversible adverse events may occur. IFN-α represents an alternative therapeutic option in cases of refractory to standard treatment.

Cis-9,trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial cells and eosinophils: comparison to trans-10,cis-12-CLA and to linoleic acid.

Interaction of eosinophils and bronchial epithelial cells plays a pivotal role in maintaining inflammatory airway disease. Since conjugated linoleic acids (CLA) are suggested to exert anti-inflammatory effects, one purpose of this study was to compare cis-9,trans-11-CLA and trans-10,cis-12-CLA with regard to their influence on the stimulus-induced activation of eosinophils. ECP (eosinophil cationic protein) released in co-culture of stimulated and CLA-treated eosinophils with stimulated bronchial epithelial cells (BEAS-2B) was measured and cis-9,trans-11-CLA was found to be most potent in inhibiting ECP formation. Further, expression of the activation markers CD69 and CD13 induced by various stimuli (TNF-alpha, IL-5, IL-3) was significantly reduced in the presence of cis-9,trans-11-CLA. Subsequently, various concentrations of cis-9,trans-11-CLA vs. linoleic acid (LA, cis-9,cis-12-octadecadienoic acid) were tested for the effect on proliferative response and release of the pro-inflammatory cytokine IL-8 in stimulated BEAS-2B. Addition of cis-9,trans-11-CLA attenuated cell growth and significantly reduced IL-8 production at mRNA and protein levels. In contrast, LA had a slight stimulating effect on proliferation and was less effective in reducing the cytokine release. It was demonstrated that the inhibitory effect of cis-9,trans-11-CLA on IL-8 production is mediated through activation of the nuclear receptor PPARgamma, since blocking the receptor with a selective antagonist (GW9662) restored the stimulus-induced enhancement in IL-8 mRNA expression and protein secretion. PPARgamma has previously been shown to be closely involved in the downregulation of inflammation during hyperresponsiveness related to pulmonary immune responses. Thus, targeting PPARgamma, cis-9,trans-11-CLA might be of therapeutic value in the focus of airway disease while ameliorating inflammatory processes by affecting epithelial and eosinophil functions.

Anthracofibrosis Manifesting as False-Positive Iodine Accumulation in a Patient With Recent History of Thyroid Carcinoma.

A 33-year-old Indonesian woman presented for follow-up after a recent history of papillary thyroid carcinoma treated with total thyroidectomy and radioiodine therapy. A 131I whole-body scintigraphy showed an elongated iodine accumulation in the right hemithorax. On suspicion of pulmonary metastasis, further diagnostics with 124I PET/CT showed thickening of the bronchial wall and retention of secretion in a middle lobe bronchus. Bronchoscopy and histology allowed a diagnosis of stenosing anthracofibrosis with chronic inflammatory changes.

Expression and synthesis of fibroblast growth factor-9 in human gammadelta T-lymphocytes. Response to isopentenyl pyrophosphate and TGF-beta1/IL-15.

Gammadelta T-lymphocytes are believed to play a role in maintaining the normal configuration of epithelial tissue. As little is known about the factors mediating this function, we addressed the question of whether gammadelta T-lymphocytes produce fibroblast growth factor (FGF)-9 as well as two other growth factors associated with epithelial tissue reconstitution. Blood gammadelta T cells isolated from healthy donors were grown in the presence of isopentenyl pyrophosphate (IPP) or transforming growth factor-beta1 (TGF-beta1)/interleukin-15 (IL-15) for 24 h and were assessed for the expression and synthesis of FGF-9, keratinocyte growth factor (KGF), and epidermal growth factor (EGF). Resting human gammadelta T cells constitutively expressed KGF and FGF-9 mRNA but no EGF mRNA. In the presence of IPP, FGF-9 mRNA expression significantly increased in a dose-dependent manner, expression of KGF remained unaltered, and EGF mRNA could not be detected. In contrast to IPP, stimulation of the cells with TGF-beta1/IL-15 did not alter FGF-9 expression. Moreover, stimulation with anti-CD3 does not induce FGF-9 expression but triggers a high signal of interferon-gamma mRNA. Western blot analysis of gammadelta T cell lysates, prepared 4 days following stimulation with IPP, showed an increase of FGF-9 protein as compared with control cells. In conclusion, the results demonstrate for the first time that human blood and bronchoalveolar lavage gammadelta T-lymphocytes are capable of expressing FGF-9. The data also provide novel evidence that immunoregulatory cells can synthesize FGF-9.

Accuracy of transthoracic sonography in excluding post-interventional pneumothorax and hydropneumothorax. Comparison to chest radiography.

OBJECTIVE: Transthoracic sonography (TS) has evolved as an important imaging technique for diagnosing pleural and pulmonary conditions. However, the value of TS in either excluding or diagnosing pneumothorax is still under debate. This study was conducted to examine whether TS could replace chest radiography for the diagnosis of post-interventional pneumothorax and hydropneumothorax. METHODS: 53 patients (21 females, 32 males; median age 64 years, range 37-94 years), 35 of whom underwent transbronchial biopsy (TBB) and 18 patients who had an ultrasound-guided chest tube placement (U-GCTP) were enrolled in the study. TS was performed three hours after either TBB or removal of a chest tube, followed by postero-anterior chest radiograph (CRX). If any discrepancy between TS, the clinical presentation and the CRX became apparent, either a lateral CRX or a computed tomography (CT) of the thorax was performed. TS was assessed according to the presence of the following criteria: (1) "gliding sign" of the pleural line, (2) comet tail artifacts, (3) reverberation artifacts, (4) air/fluid mirror, (5) hyperechoic reflectors within the pleural effusion and (6) "lung point". RESULTS: In four out of the 53 patients (7.5%) a post-interventional pneumothorax or hydropneumothorax occurred. One out of the 35 patients (2.9%) developed a pneumothorax after TBB, requiring chest tube placement. Three patients (16.7%) developed a hydropneumothorax due to U-GCTP which was detected by sonography but was missed by postero-anterior CRX in one patient. The sensitivity, specificity and accuracy of TS were 100% in excluding post-interventional pneumothorax/hydropneumothorax. CONCLUSION: TS is a cost-effective and safe bed-side-method, allowing for an immediate exclusion or diagnosis of post-interventional pneumothorax/hydropneumothorax in patients who have undergone TBB or U-GCTP. Thus, these preliminary results suggest that CXR may only be required in patients with pneumothorax diagnosed by TS in order to assess its extension or to exclude any discrepancy between the TS-result and the clinical presentation.

Dual Transmembrane Signalling Mechanisms in Eosinophils: Evidence for Two Functionally Distinct Receptors for Platelet-Activating Factor.

The effect of PAF on eosinophil activation was investigated. TxB2 release required a lower concentration of PAF (ED50 = 17.2 nM) whereas for superoxide anion (O2) production doses in excess of 1 µM (ED50 = 31.7 µM) were needed. The PAF-induced O2 release occurred in the absence of increased [Ca2+]i whereas the production of TxB2 paralleled the magnitude of the [Ca2+]i increase. Pretreatment of the eosinophils with pertussis toxin (PTX) reduced both the PAF-induced release of TxB2 and the PAF-induced rise in [Ca2+]i. However, PTX failed to inhibit PAF-induced O2 generation. Experiments with the microsomal (100,000 g) fraction from these cells demonstrated that PTX pretreatment had ADP-ribosylated a 41-kD protein in the membrane, confirming that GTP binding proteins are present in eosinophil membranes. Scatchard plot analysis of radioligand binding to eosinophil membranes indicated the presence or two binding sites with an apparent Kd of 0.33 and 11.5 nM, respectively. The results suggest that two distinct forms of the PAF receptor can be identified in eosinophil membranes.

Phenotypic and molecular characterization of CD103+ CD4+ T cells in bronchoalveolar lavage from patients with interstitial lung diseases.

BACKGROUND: The integrin CD103 is preferentially expressed on intraepithelial T lymphocytes, and cells expressing this integrin may play a regulatory role in the microenvironment of the epithelial cell layer. METHODS: The relative number of CD103(+)/CD4(+) T cells in the bronchoalveolar lavage was significantly elevated in all patients diagnosed with interstitial lung diseases compared with patients with other non-fibrotic disorders of the lung. RESULTS: Analysis by flow cytometry showed that the CD103(+) and the CD103(-) subpopulations were memory T cells based on the high expression of CD45RO(+). However, the CD103(+)/CD4(+) T cells were CD25(low), CD27(-), CD28(low), and CD62L(-), whereas the CD103(-)/CD4(+) T cells expressed CD25 and CD62L and were CD27(high) and CD28(high). In addition, the CD103(+)/CD4(+) T cells expressed significantly higher quantities of VLA-1 and CD101 than did CD103(-)/CD4(+) T cells. Reverse transcriptase polymerase chain reaction analysis of purified CD103(+) and CD103(-) CD4(+) T cells showed production of tumor necrosis factor (TNF) alpha-R-1 (p55), TNF-alpha-R-2 (p75), interferon gamma, interleukin-10, and TNF-alpha mRNA in both subpopulations. No interleukin-4 mRNA was detected in either subpopulation. CONCLUSIONS: CD103(+)/CD4(+) T cells represent a T-helper 1-like subpopulation in human lungs with a distinct effector phenotype. Despite the lack of CD27 and the low CD25 and CD28 expression, these cells show a high degree of activation. These results suggest that CD103 expressing CD4 T cells in the lung are continuously activated, long-living cells.

Ancillary lung parenchymal findings at spiral CT scanning in pulmonary embolism. Relationship to chest sonography.

INTRODUCTION/OBJECTIVE: The aim of the study was to compare findings of transthoracic sonography (TS) and of spiral computed tomography (sCT) in patients with suspected pulmonary embolism (PE). METHODS AND PATIENTS: Peripheral parenchymal and pleural findings of TS and sCT were compared in 62 patients (25 females, 37 males; mean age 62.2 years) with suspected PE. RESULTS: In 39 patients PE was established, of whose pleura-based lesions could be detected by TS in 30 patients and by sCT in 31 patients. Whilst in three of the patients parenchymal lesions were exclusively detected by sonography, no peripheral abnormalities could be discovered with either technique in five patients. Among the nine patients lacking peripheral abnormalities on sonography, four revealed peripheral lesions in sCT. In 23 patients without PE, peripheral consolidations at CT were detected in six patients whereas two showed lesions on TS. With respect to the appearance, pleura-based wedge-shaped consolidations were the main parenchymal alterations (82.4% at TS, 66.1% at sCT) as compared with non-wedge-shaped consolidations (17.6% at TS, 33.9% at sCT). Peripheral lesions were located preferentially within the lower lobes. In addition, both localised and basal pleural effusion associated with PE could be demonstrated in 58.9% at TS and in 23.1% by sCT. DISCUSSIONS AND CONCLUSION: The study shows that in PE parenchymal and pleural changes are detectable by TS and sCT. If parenchymal findings are present at sCT, peripheral PE should be considered, even in the absence of directly visible emboli.

Omalizumab in patients with severe asthma: the XCLUSIVE study.

BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice-related setting is limited. Thus, the purpose of this prospective multi-centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real-life clinical practice in Germany. METHODS: One hundred ninety-five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed. RESULTS: Measured outcome variables improved after a 16-week treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate -74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder). Responders demonstrated better improvement of FEV(1), exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non-responders. CONCLUSION: Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice-related setting.

Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study.

BACKGROUND: The aim of this prospective, multicenter study was to define the accuracy of lung ultrasound (LUS) in the diagnosis of community-acquired pneumonia (CAP). METHODS: Three hundred sixty-two patients with suspected CAP were enrolled in 14 European centers. At baseline, history, clinical examination, laboratory testing, and LUS were performed as well as the reference test, which was a radiograph in two planes or a low-dose CT scan in case of inconclusive or negative radiographic but positive LUS findings. In patients with CAP, follow-up between days 5 and 8 and 13 and 16 was scheduled. RESULTS: CAP was confirmed in 229 patients (63.3%). LUS revealed a sensitivity of 93.4% (95% CI, 89.2%-96.3%), specificity of 97.7% (95% CI, 93.4%-99.6%), and likelihood ratios (LRs) of 40.5 (95% CI, 13.2-123.9) for positive and 0.07 (95% CI, 0.04-0.11) for negative results. A combination of auscultation and LUS increased the positive LR to 42.9 (95% CI, 10.8-170.0) and decreased the negative LR to 0.04 (95% CI, 0.02-0.09). We found 97.6% (205 of 211) of patients with CAP showed breath-dependent motion of infiltrates, 86.7% (183 of 211) an air bronchogram, 76.5% (156 of 204) blurred margins, and 54.4% (105 of 193) a basal pleural effusion. During follow-up, median C-reactive protein levels decreased from 137 mg/dL to 6.3 mg/dL at days 13 to 16 as did signs of CAP; median area of lesions decreased from 15.3 cm2 to 0.2 cm2 and pleural effusion from 50 mL to 0 mL. CONCLUSIONS: LUS is a noninvasive, usually available tool used for high-accuracy diagnosis of CAP. This is especially important if radiography is not available or applicable. About 8% of pneumonic lesions are not detectable by LUS; therefore, an inconspicuous LUS does not exclude pneumonia.