Simultaneous Multifocal Intracranial Haemorrhages Associated with Staphylococcus Aureus Endocarditis: A Plausible Role for Diclofenac Administration.

Introduction: Intracranial haemorrhage may complicate infective endocarditis, caused by ruptured mycotic aneurysms or haemorrhagic transformation of brain septic emboli. The risk of intracranial bleeding may increase with the use of non-steroidal anti-inflammatory agent (NSAIDs). Case description: We report on a 53-year-old male patient with a past history of intravenous drug abuse, who was treated with diclofenac (75 mg IM) for a few hours of preceding fever and arthralgia. Seven hours later he was hospitalised with impaired consciousness and hemiparesis. Evaluation revealed multiple intracranial haemorrhages, at least one originating from a mycotic aneurysm. Repeated blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and echocardiography revealed a vegetation on the mitral valve, establishing the diagnosis of bacterial endocarditis. Conclusion: The abrupt simultaneous multifocal intracranial bleeds shortly following the administration of NSAIDs for a few hours of febrile disease, one clearly originating from a mycotic aneurism, are exceptional. This raises a possibility of a role for diclofenac the intracranial bleeding diathesis in this unique clinical presentation. Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis (IE) might be added to the long list of potential adverse outcomes of NSAID administration, and the possibility of IE should be considered before their administration for febrile disease of undetermined cause. LEARNING POINTS: Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis might be added to the long list of potential adverse outcomes of NSAID administration.The possibility of infective endocarditis should be considered before the administration of NSAIDs for febrile disease of an undetermined cause.

Association of the risk of obstructive sleep apnoea with the severity of COVID-19.

Patients with coronavirus 2019 (COVID-19) and obstructive sleep apnoea (OSA) have a worse prognosis than COVID-19 patients without OSA. This study aimed to examine the relationship between OSA risk and the severity of COVID-19 in patients undiagnosed with OSA. Patients diagnosed with COVID-19 and hospitalized or admitted to a community hotel were recruited for the study after recovery during a clinic check-up visit 6-8 weeks after discharge. At this visit, they answered the Epworth Sleeping Scale (ESS) and Berlin questionnaire. Demographic and clinical details were collected from electronic medical records. OSA risk was observed in 37 of 119 included patients (31.1%). Patients with high OSA risk were male, significantly older, had a higher body mass index (BMI), and had higher rates of hypertension and snoring than patients with low OSA risk. Moreover, OSA risk was associated with COVID-19 severity; 48.6% of patients with high risk for OSA suffered from severe COVID-19 compared to 22% of patients with low risk for OSA (p = 0.007). The duration of hospitalization for patients with a high OSA risk was 10.97±9.43 days, while that for those with a low OSA risk was 4.71±6.86 days (p = 0.001). After adjusting for BMI, age, hypertension, and chronic disease, the odds ratio was 4.3 (95%CI, 1.2-16, p = 0.029). A high OSA risk was associated with severe COVID-19 and longer hospitalization. Thus, we recommend that the Berlin and ESS questionnaires be completed for every COVID-19-infected patient at hospitalization, especially in the presence of comorbidities.

Clinical Use of an Exposure, Symptom, and Spirometry Algorithm to Stratify Smokers into COPD Risk Phenotypes: A Case Finding Study Combined with Smoking Cessation Counseling.

Background: Chronic obstructive pulmonary disease (COPD) case-finding aims to detect airflow obstruction in symptomatic smokers and ex-smokers. We used a clinical algorithm including smoking, symptoms, and spirometry to classify smokers into COPD risk phenotypes. In addition, we evaluated the acceptability and effectiveness of including smoking cessation advice in the case-finding intervention. Methods: Smoking, symptoms, and spirometry abnormalities (airflow obstruction: forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] <0.7 or preserved-ratio spirometry (FEV1<80% of predicted value and FEV1/FVC ratio ≥ 0.7)] were assessed in a group of 864 smokers aged ≥ 30 years. The combination of these parameters allowed the identification of 4 phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms; normal spirometry; possible COPD), Phenotype C (no symptoms; abnormal spirometry; possible COPD), and Phenotype D (symptoms; abnormal spirometry; probable COPD). We assessed phenotype differences in clinical variables and modeled the trend from phenotype A to phenotype D. Smoking cessation advice based on spirometry was provided. Follow-up was done by telephone 3 months later. Results: Using smokers without symptoms or abnormal spirometry (phenotype A; n=212 [24.5%]) as a reference, smokers were classified into possible COPD (phenotype B;n=332 [38.4%]; and C: n=81 [9.4%]) and probable COPD (phenotype D: n=239 [27.2%]). The trend from baseline phenotype A to probable COPD phenotype D was significant for the number of cigarettes/day and the number of years of smoking (p=0.0001). At follow-up, 58 (7.7%) of the respondents (n=749) reported that they had quit smoking. Conclusions: Our clinical algorithm allowed us to classify smokers into COPD phenotypes whose manifestations were associated with smoking intensity and to significantly increase the number of smokers screened for COPD. Smoking cessation advice was well accepted, resulting in a low but clinically significant quit rate.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.

BACKGROUND: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. OBJECTIVES: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. METHODS: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. RESULTS: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. CONCLUSIONS: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.

The DNA methylome of human vascular endothelium and its use in liquid biopsies.

BACKGROUND: Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover. METHODS: To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues. FINDINGS: A comparison with a human cell-type methylome atlas yielded thousands of loci that are uniquely unmethylated in VECs. These sites are typically gene enhancers, often residing adjacent to VEC-specific genes. We also identified hundreds of genomic loci that are differentially methylated in organotypic VECs, indicating that VECs feeding specific organs are distinct cell types with a stable epigenetic identity. We established universal and lung-specific VEC markers and evaluated their presence in circulating cell-free DNA (cfDNA). Nearly 2.5% of cfDNA in the plasma of healthy individuals originates from VECs. Sepsis, graft versus host disease, and cardiac catheterization are associated with elevated levels of VEC-derived cfDNA, indicative of vascular damage. Lung-specific VEC cfDNA is selectively elevated in patients with chronic obstructive pulmonary disease (COPD) or lung cancer, revealing tissue-specific vascular turnover. CONCLUSIONS: VEC cfDNA biomarkers inform vascular dynamics in health and disease, potentially contributing to early diagnosis and monitoring of pathologies, and assessment of drug activity. FUNDING: This work was supported by the Beutler Research Program, Helmsley Charitable Trust, JDRF, Grail and the DON Foundation (to Y.D.). Y.D holds the Walter & Greta Stiel Chair in heart studies. B.G., R.S., J.M., D.N., T.K., and Y.D. filed patents on cfDNA analysis.

Prevalence and Persistence of Symptoms in Adult COVID-19 Survivors 3 and 18 Months after Discharge from Hospital or Corona Hotels.

COVID-19 is characterized by persistent symptoms beyond acute illness. In this prospective cohort study of patients with COVID-19, we sought to characterize the prevalence and persistence of symptoms up to 18 months after diagnosis. We followed 166 patients and assessed their symptoms during acute illness, and at 3 and 18 months after disease onset. The mean number of symptoms per patient during acute disease was 2.3 (SD:1.2), dropping to 1.8 (SD:1.1) at 3 months after recovery and to 0.6 (SD:0.9) at 18 months after recovery. However, this decrease was not unidirectional. Between acute illness and 3 months, the frequency of symptoms decreased for cough (64.5%→24.7%), ageusia (21.7% to6%), anosmia (17.5%→5.4%), and generalized pain (10.8% to 5.4%) but increased for dyspnea (53%→57.2%) weakness (47%→54.8%), and brain fog (3%→8.4%). Between 3 and 18 months, the frequency of symptoms decreased for all symptoms but remained relatively high for dyspnea (15.8%), weakness (21.2%), and brain fog (7.3%). Symptoms may persist for at least 18 months after acute COVID-19 infection. During the medium- to long-term recovery period, the prevalence of some symptoms may decrease or remain stable, and the prevalence of others may increase before slowly decreasing thereafter. These data should be considered when planning post-acute care for these patients.

Varenicline for Gradual Versus Abrupt Smoking Cessation in Poorly Motivated Smokers With COPD: A Prematurely Terminated Randomized Controlled Trial.

Background: Although smoking is the leading cause of chronic obstructive pulmonary disease (COPD), many patients with COPD smoke, highlighting the need for effective smoking cessation interventions in this population. This study examined the efficacy and safety of varenicline in increasing smoking cessation rates through "gradual" versus "abrupt" cessation in COPD patients with low motivation to quit smoking. Methods: A randomized, open label, 30-week, controlled trial (ClinicalTrials.gov identifier: NCT02894957) was conducted between January 2019 and October 2020 at a center in Israel. Smokers with COPD, poorly motivated to quit, were randomized to 6 weeks of varenicline for smoking reduction and a target quit day (TQD) at the end of week 6 (gradual cessation group) or ad libitum smoking for 5 weeks, 1 week of varenicline, and a TQD at the end of week 6 (abrupt cessation group). After the pre-quit phase, both groups received 12-week regular varenicline treatment and 12-week follow-up. Primary outcome was biochemically-validated continuous abstinence for weeks 6-30. Secondary outcomes were: (1) biochemically-confirmed7-day point prevalence abstinence for weeks 4-30, (2) efficient smoking reduction (≥50% in number of cigarettes/day) in the pre-quit phase; and (3) number of cigarettes/day, motivation to quit, and changes in respiratory symptoms and spirometry from baseline through week 30. Results: A drug recall issued by the study sponsor stopped the study after 70/242 (28.9%) patients had been enrolled. The gradual cessation group (n=29) had significantly higher continuous abstinence rates from TQD through week 30 versus the abrupt cessation group (n=41): 20.7% versus 4.9% (odds ratio [OR]=5.09; 95% confidence interval [CI] 0.89-29.17; p=0.048) and higher 7-day point prevalence abstinence levels at all time points but week 18 (p=0.027 at week 6, 0.056 at week 7, and 0.096 at week 9). Motivation to quit increased (p=0.002) and the number of cigarettes/day decreased (p=0.002) over time in both groups. Respiratory symptoms, but not spirometry, improved in both groups at week 30. Treatment was safe and well tolerated. Conclusion: In poorly motivated smokers with COPD, using varenicline for a 6-week gradual smoking cessation before TQD, compared with abrupt cessation, significantly increased quit rates up to 6 months. Results were not affected by the smaller-than-expected sample size. Further studies are needed to confirm these data.

Universal lung epithelium DNA methylation markers for detection of lung damage in liquid biopsies.

BACKGROUND: Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA (cfDNA) in blood, as an indication of lung cell death. METHODS: We sorted human lung alveolar and bronchial epithelial cells from surgical specimens, and obtained their methylomes using whole-genome bisulfite sequencing. We developed a PCR sequencing assay determining the methylation status of 17 loci with lung-specific methylation patterns, and used it to assess lung-derived cfDNA in the plasma of healthy volunteers and patients with lung disease. RESULTS: Loci that are uniquely unmethylated in alveolar or bronchial epithelial cells are enriched for enhancers controlling lung-specific genes. Methylation markers extracted from these methylomes revealed that normal lung cell turnover probably releases cfDNA into the air spaces, rather than to blood. People with advanced lung cancer show a massive elevation of lung cfDNA concentration in blood. Among individuals undergoing bronchoscopy, lung-derived cfDNA is observed in the plasma of those later diagnosed with lung cancer, and to a lesser extent in those diagnosed with other lung diseases. Lung cfDNA is also elevated in patients with acute exacerbation of COPD compared with patients with stable disease, and is associated with future exacerbation and mortality in these patients. CONCLUSIONS: Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.

Liquid biopsy reveals collateral tissue damage in cancer.

Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases. In addition, patients with localized pancreatic or colon cancer showed elevated hepatocyte cfDNA, suggesting liver damage inflicted by micrometastatic disease, by primary pancreatic tumor pressing the bile duct, or by a systemic response to the primary tumor. We also identified elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA in a subpopulation of patients with brain metastases compared with cancer patients without brain metastasis. Cell type-specific cfDNA methylation markers enabled the identification of collateral tissue damage in cancer, revealing the presence of metastases in specific locations and potentially assisting in early cancer detection.

Diffuse pulmonary calcifications: A case series and review of literature.

Pulmonary calcifications are usually incidental asymptomatic findings discovered on x-rays or computed tomography scans that can be easily overlooked, and their significance undermined, especially in a seemingly asymptomatic person. Calcifications can be a marker of chronicity or disease severity, and thus have diagnostic value. Rarely, calcification can be the direct cause of morbidity. Calcifications can be either localized or diffuse. Many diseases, in particular infectious diseases, can cause localized calcifications. Diffuse calcifications are less common and usually secondary to a handful of conditions such as dystrophic pulmonary calcifications, metastatic pulmonary calcifications, disseminated pulmonary ossifications and pulmonary alveolar microlithiasis. We describe three cases of diffuse pulmonary calcifications, review the different causes of diffuse pulmonary calcifications and provide some indicators on how to differentiate between them. Differentiating between the different types of pulmonary calcifications has significant implications on the management and prognosis of the patients, and thus it is important to distinguish between them.

Early Detection of COPD: An Opportunistic Case Finding Study in Smokers and Ex-Smokers Visiting a Medical Centre.

BACKGROUND: Different case finding approaches have been used to identify early COPD. The objective of this study was to assess the feasibility and the yield of opportunistic early COPD case finding in visitors to a large medical centre. PATIENTS AND METHODS: From May 2014 to June 2017, we consecutively recruited adults aged ≥ 18 years visiting the Shaare Zedek Medical Center, in Jerusalem. Our 3-step intervention included: a) pre-screening for symptoms with the 5-item "Could it be COPD?" questionnaire (score= 0-5 pts); b) pre-BD spirometry; and c) referral to a caregiver. Airflow obstruction was defined by a FEV1/FVC < 0.7. Spirometry results were used as an incentive to promote smoking cessation and quit rates were verified by phone survey 3 months after the intervention. RESULTS: A total of 1001 subjects (956 smokers; 45 ex-smokers) were recruited. Mean (SD) age was 48.3 years (13.5). Airflow obstruction was detected in 180 (18%) subjects of whom 142 (78.9%) were unaware of it, including 27 subjects with severe (50% ≥ FEV1 ≤ 30% predicted) (n=25) or very severe (FEV1 < 30% predicted) (n=2) obstruction. Multiple logistic regression analysis found that age, BMI, cigarette smoking (p.y.) and a "Could it be COPD?" questionnaire score ≥ 3 points correctly classified 83.3% of cases of airflow obstruction. At follow-up, 54.5% of participants reported smoking as usual, 30.9% reduced smoking [mean (SD) = 10.1 ± 7.8 cigarettes/day], 7.4% increased smoking [mean (SD) = 9.2 ± 6.3 cigarettes/day] and 7.2% claimed smoking cessation. Among obstructed subjects, 38.7% had visited a physician because of COPD, while 20.7% were taking a new respiratory medication. CONCLUSION: Early COPD case finding was feasible and effective in identifying undiagnosed airflow obstruction among visitors to a medical centre. Smoking cessation counselling based on spirometry promoted a small but clinically meaningful cessation rate.

[DIAPHRAGMATIC PARALYSIS].

INTRODUCTION: One-sided diaphragmatic paralysis is a common phenomenon which is usually a-symptomatic. In case of acute onset or if there is an underlying lung disease, the phenomenon may be symptomatic and even limiting. In this article, we present a patient who arrived with subacute shortness of breath when lying down. She underwent thorough investigations but, as happens in most cases, the cause of the paralysis was not identified and it remains idiopathic. The authors present an overview of the etiology, differential diagnosis and treatment of diaphragmatic paralysis.

Influence of language skills on the choice of terms used to describe lung sounds in a language other than English: a cross-sectional survey of staff physicians, residents and medical students.

INTRODUCTION: The value of chest auscultation would be enhanced by the use of a standardised terminology. To that end, the recommended English terminology must be transferred to a language other than English (LOTE) without distortion. OBJECTIVE: To examine the transfer to Hebrew-taken as a model of LOTE-of the recommended terminology in English. DESIGN/SETTING: Cross-sectional study; university-based hospital. PARTICIPANTS: 143 caregivers, including 31 staff physicians, 65 residents and 47 medical students. METHODS: Observers provided uninstructed descriptions in Hebrew and English of audio recordings of five common sounds, namely, normal breath sound (NBS), wheezes, crackles, stridor and pleural friction rub (PFR). OUTCOMES: (a) Rates of correct/incorrect classification; (b) correspondence between Hebrew and recommended English terms; c) language and auscultation skills, assessed by crossing the responses in the two languages with each other and with the classification of the audio recordings validated by computer analysis. RESULTS: Range (%) of correct rating was as follows: NBS=11.3-20, wheezes=79.7-87.2, crackles=58.6-69.8, stridor=67.4-96.3 and PFR=2.7-28.6. Of 60 Hebrew terms, 11 were correct, and 5 matched the recommended English terms. Many Hebrew terms were adaptations or transliterations of inadequate English terms. Of 687 evaluations, good dual-language and single-language skills were found in 586 (85.3%) and 41 (6%), respectively. However, in 325 (47.3%) evaluations, good language skills were associated with poor auscultation skills. CONCLUSION: Poor auscultation skills surpassed poor language skills as a factor hampering the transfer to Hebrew (LOTE) of the recommended English terminology. Improved education in auscultation emerged as the main factor to promote the use of standardised lung sound terminology. Using our data, a strategy was devised to encourage the use of standardised terminology in non-native English-speaking countries.

Identification of Asthma-COPD Overlap, Asthma, and Chronic Obstructive Pulmonary Disease Phenotypes in Patients with Airway Obstruction: Influence on Treatment Approach.

BACKGROUND: Many studies have described asthma-COPD overlap (ACO) among patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), but less so in broad populations of patients with chronic airway obstruction. OBJECTIVE: This study aimed to (i) examine the prevalence of ACO, asthma, and COPD phenotypes among subjects referred for pulmonary function testing (PFT), who had airway obstruction in spirometry (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] <0.7); and (ii) delineate the therapeutic approach of each group. METHODS: Cross-sectional study of patients who were referred for PFT at the Rokach Institute, in Jerusalem. Working definitions were as follows: (a) COPD: post-bronchodilator (BD) FEV1/FVC <0.70; (b) asthma: physician-diagnosed asthma before age 40 and/or minimum post-BD increase in FEV1 or FVC of 12% and 200 mL; and (c) ACO: the combination of the 2. Demographics, smoking habits, episodes of exacerbation, health-related quality of life (HRQL), and respiratory medication utilization were analyzed. RESULTS: Of 3,669 referrals from January 1 to April 30, 2017, 1,220 had airway obstruction of which 215 were included. Of these, 82 (38.1%) had ACO, 49 (22.8%) asthma, and 84 (39.1%) COPD. ACO subjects tended to (a) be predominantly female; (b) be older than asthmatics, (c) be smokers; (d) have worse HRQL in the activity domain; and (d) have more exacerbations. Treatment of ACO and COPD patients differed from that of asthmatics, but not from each other, in the proportion of subjects on maintenance treatment, use of LABA, LAMA, and ICS, alone or in combination, and in the number of inhaler devices used by patients. CONCLUSION: ACO represented >1/3 of patients referred for PFT. Despite a clearly identifiable phenotype, ACO patients received treatment similar to COPD patients, suggesting poor ACO identification. Our data emphasize the need to raise the awareness of ACO among clinicians, in order to guide better recognition and appropriate treatment in individual patients.

The Effect of Pulmonary Rehabilitation on Non-chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Pulmonary rehabilitation has shown significant benefit for patients with chronic obstructive pulmonary disease (COPD). The effect on non-COPD pulmonary patients is less well established. OBJECTIVES: To determine whether pulmonary rehabilitation is also beneficial for non-COPD pulmonary patients. METHODS: Clinical and demographic data on non-COPD pulmonary patients who participated in our institutional pulmonary rehabilitation program between January 2009 and December 2016 were collected. Participants engaged in a 60-minute, twice-weekly, ambulatory hospital-based program lasting 12 to 24 sessions. Sessions included both endurance and muscle training as well as healthy lifestyle educational activities. The six-minute walk test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) were conducted before and after the rehabilitation program. RESULTS: We recruited 214 non-COPD patients, of whom 153 completed at least 12 sessions. Of these, 59 presented with interstitial lung disease (ILD), 18 with non-ILD restrictive lung defects, 25 with asthma, 30 with lung cancer, and 21 with other conditions (e.g., pulmonary hypertension, bronchiectasis) The groups demonstrated significant improvement in 6MWT and in SGRQ scores. Non-COPD patients gained a 61.9 meter (19%) improvement in the 6MWT (P < 0.0001) and 8.3 point reduction in their SGRQ score (P < 0.0001). CONCLUSIONS: Pulmonary rehabilitation is effective in non-COPD pulmonary patients. As such, it should be an integral part of the treatment armament provided to the vast majority of those suffering from chronic respiratory disease.

The effect of body position on pulmonary function: a systematic review.

BACKGROUND: Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the influence of body position on lung function in healthy persons and specific patient groups. METHODS: A search to identify English-language papers published from 1/1998-12/2017 was conducted using MEDLINE and Google Scholar with key words: body position, lung function, lung mechanics, lung volume, position change, positioning, posture, pulmonary function testing, sitting, standing, supine, ventilation, and ventilatory change. Studies that were quasi-experimental, pre-post intervention; compared ≥2 positions, including sitting or standing; and assessed lung function in non-mechanically ventilated subjects aged ≥18 years were included. Primary outcome measures were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC, FEV1/FVC), vital capacity (VC), functional residual capacity (FRC), maximal expiratory pressure (PEmax), maximal inspiratory pressure (PImax), peak expiratory flow (PEF), total lung capacity (TLC), residual volume (RV), and diffusing capacity of the lungs for carbon monoxide (DLCO). Standing, sitting, supine, and right- and left-side lying positions were studied. RESULTS: Forty-three studies met inclusion criteria. The study populations included healthy subjects (29 studies), lung disease (nine), heart disease (four), spinal cord injury (SCI, seven), neuromuscular diseases (three), and obesity (four). In most studies involving healthy subjects or patients with lung, heart, neuromuscular disease, or obesity, FEV1, FVC, FRC, PEmax, PImax, and/or PEF values were higher in more erect positions. For subjects with tetraplegic SCI, FVC and FEV1 were higher in supine vs. sitting. In healthy subjects, DLCO was higher in the supine vs. sitting, and in sitting vs. side-lying positions. In patients with chronic heart failure, the effect of position on DLCO varied. CONCLUSIONS: Body position influences the results of PFTs, but the optimal position and magnitude of the benefit varies between study populations. PFTs are routinely performed in the sitting position. We recommend the supine position should be considered in addition to sitting for PFTs in patients with SCI and neuromuscular disease. When treating patients with heart, lung, SCI, neuromuscular disease, or obesity, one should take into consideration that pulmonary physiology and function are influenced by body position.

Avoiding Routine Chest Radiography after Transbronchial Biopsy Is Safe.

BACKGROUND: Fiberoptic bronchoscopy (FOB) with transbronchial biopsy (TBB) is complicated by a pneumothorax in 1-4% of cases. Performance of routine post-TBB chest radiography (CXR) results in an extremely low diagnostic yield but nevertheless is the common clinical practice prevailing today. It has previously been suggested that routine post-TBB CXR could be avoided in asymptomatic patients. OBJECTIVE: The objective of this study was to prospectively assess the feasibility and safety of this approach. METHODS: The study group included 201 consecutive patients who underwent FOB with TBB at our institution between January 2009 and September 2014. All subjects completed a preprocedural, a 2-hour postprocedural, and a 24- to 48-hour postprocedural symptom questionnaire (chest pain, dyspnea, and cough). Post-TBB CXR was ordered by the treating physician only if indicated. All cases of pneumothorax were documented. Additionally, the following information was recorded: sex, age, immune status, indication for FOB, total number of biopsies done, lobe sampled, and pulse oxygen saturation. RESULTS: Sixteen CXRs were ordered by the treating physician due to suspected pneumothorax (8%). Early-onset pneumothorax (i.e. within 2 h of TBB) was diagnosed radiologically in 6 patients (3%). Two late-onset pneumothoraxes (1%) were diagnosed more than 24 h after TBB. No pneumothoraxes of clinical significance were diagnosed among asymptomatic patients without significant oxygen desaturation events. CONCLUSIONS: Among asymptomatic patients without significant desaturation events, pneumothorax is rare and usually of negligible clinical significance. Therefore, performance of routine CXR after TBB is not necessary and can be safely avoided in this category of patients.