Classically, mitochondria have largely been believed to influence the development of illness by modulating cell metabolism and determining the rate of production of high-energy phosphate compounds (eg, adenosine triphosphate). It is now recognized that this view is simplistic and that mitochondria play key roles in many other processes, including cell signaling, regulating gene expression, modulating cellular calcium levels, and influencing the activation of cell death pathways (eg, caspase activation). Moreover, these multiple mitochondrial functional characteristics are now known to influence the evolution of cellular and organ function in many disease states, including sepsis, ICU-acquired skeletal muscle dysfunction, acute lung injury, acute renal failure, and critical illness-related immune function dysregulation. In addition, diseased mitochondria generate toxic compounds, most notably released mitochondrial DNA, which can act as danger-associated molecular patterns to induce systemic toxicity and damage multiple organs throughout the body. This article reviews these evolving concepts relating mitochondrial function and acute illness. The discussion is organized into four sections: (1) basics of mitochondrial physiology; (2) cellular mechanisms of mitochondrial pathophysiology; (3) critical care disease processes whose initiation and evolution are shaped by mitochondrial pathophysiology; and (4) emerging treatments for mitochondrial dysfunction in critical illness.

Admissions to the ICU related to alcohol, prescription drugs, and illicit drugs are shown to be widespread and costly. In 1993, a study revealed 28% of ICU admissions at Johns Hopkins Hospital were related to substance abuse and accrued 39% of costs. Since then, health-care expenditures have increased, and substance abuse treatment admissions have risen. We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital in Indianapolis, Indiana.

Airway remodeling is a characteristic feature of asthma and is thought to play an important role in the pathogenesis of airway hyperresponsiveness. Myofibroblasts are key structural cells involved in injury and repair, and there is evidence that dysregulation of their normal function contributes to airway remodeling. Despite the importance of myofibroblasts, a lack of specific cellular markers and inconsistent nomenclature have limited recognition of their key role in airway remodeling. Myofibroblasts are increased several-fold in the airways in asthma, in proportion to the severity of the disease. Myofibroblasts are postulated to be derived from both tissue-resident and bone marrow-derived cells, depending on the stage of injury and the tissue. A small number of studies have demonstrated attenuation of myofibroblast numbers and also reversal of established myofibroblast populations in asthma and other inflammatory processes. In this article, we review what is currently known about the biology of myofibroblasts in the airways in asthma and identify potential targets to reduce or reverse the remodeling process. However, further translational research is required to better understand the mechanistic role of the myofibroblast in asthma.

Although the link between sleep, health, and performance has been well documented, research on this link in collegiate student athletes is still in its infancy. A large body of evidence indicates that collegiate student athletes are not obtaining enough sleep, but less is known about their sleep quality, patterns, and the impact on health and performance. Consequently, short sleep negatively affects physical and mental health, as well as several domains of performance (ie, aerobic, anaerobic, sport-specific, cognitive). The majority of studies examining the links between short sleep, health, and performance have been conducted with healthy adults or noncollegiate athlete samples; however, collegiate student athletes have demands unlike those of their nonathlete or noncollegiate athlete counterparts. Poor sleep health and sleep disorders are of increasing concern among the college athlete population and have recently been recognized by national and international sports governing bodies. The purpose of this review is to summarize the available literature on sleep and its impact on health and performance among athletes, specifically addressing gaps where little to no data is available on collegiate student athletes. Consideration is also given to evidence-based sleep interventions that have been utilized with athletes, as well as recommendations for future research and intervention development.

Central airway obstruction (CAO) is associated with significant morbidity and increased mortality. Bronchoscopic electrosurgical and laser ablative tools have proven to be safe and effective instruments for the treatment of malignant CAO. Although therapeutic modalities such as electrocautery, argon plasma coagulation, and laser have been used for decades, additional tools including radiofrequency ablation catheters continue to be developed for the treatment of CAO. These modalities are considered safe in the hands of experienced operators, although serious complications can occur. This review describes various electrosurgical and laser therapy tools used for the treatment of malignant CAO along with the specific advantages and disadvantages of each device.

Both elevated pleural elastance (E-PEL) and radiographic evidence of incomplete lung expansion following thoracentesis have been used to exclude patients with a malignant pleural effusion (MPE) from undergoing pleurodesis. This article reports on a cohort of patients with MPE in whom complete drainage was attempted with pleural manometry to determine the frequency of E-PEL and its relation with postthoracentesis radiographic findings.

Health-related quality of life (QoL) is one of the most important end points in bronchiectasis (BE). However, the majority of health-related QoL questionnaires are time-consuming or not validated in BE. The COPD Assessment Test (CAT) is an easy-to-use questionnaire. The objective of this study was to perform a complete validation of the CAT in BE.

At the recent 6th World Symposium on Pulmonary Hypertension (PH), the definition of PH was redefined to include lower pulmonary artery pressures in the setting of elevated pulmonary vascular resistance (PVR). However, the relevance of this change to subjects with PH due to left-heart disease as well as the preoperative assessment of heart transplant (HT) recipients is unknown.

The Xpert MTB/RIF (Xpert) assay has greatly improved the diagnosis of TB and identification of resistance to rifampicin (RIF). However, sensitivity of Xpert remains poor for pleural fluid detection. This study evaluated the performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison with Xpert for pleural TB diagnosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare genetic multisystem disease characterized by the nodular proliferation of smooth muscle-like LAM cells, progressive cystic changes of the lung, lymphatic abnormalities, and renal angiomyolipomas (AMLs). LAM can arise sporadically or in women with the autosomal dominant disorder, tuberous sclerosis complex (TSC), in which hamartomatous tumors of brain, heart, skin, kidney, and lung are found. LAM and TSC are caused by mutations in the TSC1 or TSC2 tumor suppressor genes leading to elevated mechanistic/mammalian target of rapamycin complex activity. Recent data indicate that T cells within LAM nodules and renal AMLs exhibit features of T-cell exhaustion, with coinhibitory receptor programmed cell death protein 1 (PD-1) expression on tumor-infiltrating T cells. Treatment of animal models of TSC and LAM with anti-PD-1 antibodies or with the combination of anti-PD-1 and anti-CTLA4 antibodies has led to remarkable results, suppressing TSC2-null tumor growth and inducing tumor rejection. Here we review our current knowledge about the potential for immunotherapy for the treatment of LAM and TSC and highlight critical unknowns and key next steps.

The development of combination antiretroviral therapies (cARTs) in the mid-1990s has dramatically modified the clinical presentation of critically ill, HIV-infected patients. Most cART-treated patients aging with controlled HIV replication are currently admitted to the ICU for non-AIDS-related events, mostly bacterial pneumonia and exacerbation of comorbidities, variably affected by chronic HIV infection (COPD, cardiovascular diseases, or solid neoplasms). Today, Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis, TB, and other severe opportunistic infections only occur in patients with unknown viral status, limited access to cART, viral resistance, or compliance issues. Acute respiratory failure, neurological disorders, and sepsis remain the main conditions that lead HIV-infected patients to the ICU, although admissions for liver diseases or acute kidney injury are increasing. Case fatality dropped substantially over the past decades, reaching figures of HIV-uninfected critically ill patients with similar demographic characteristics, comorbidities, and level of organ dysfunctions. Several other facets of critical care management have evolved in this population, including diagnostic procedures, cART management at the acute phase of critical illness, and ethical considerations. The goal of this narrative review was to depict the current evidence and emerging challenges for the management of critically ill, HIV-infected patients, almost 40 years following the onset of the AIDS epidemic.

This study aimed to identify changing spatial and temporal trends of lung cancer mortality rates (LCMRs) among subpopulations in China (according to region, age, and sex).

Effective dose (ED) is used to understand radiation-related cancer risk of CT scans. Currently, ED for low-dose CT (LDCT) lung cancer screening (LCS) is estimated by multiplying the CT scan-reported dose-length product (DLP) by a DLP-to-ED conversion factor (k-factor) for general chest CT imaging, which does not account for sex. The purpose of this study was to calculate sex-specific k-factors for LDCT LCS.

Absence of interlobar collateral ventilation is key to successful endobronchial valve treatment in patients with severe emphysema and can be functionally assessed by using the Chartis measurement. This system has been validated during spontaneous breathing, undergoing procedural sedation (PS), but can also be performed under general anesthesia. Performing the Chartis measurement under PS is often challenging because of coughing, mucus secretion, and difficulties in maintaining an adequate level of sedation. The objective of this study was to investigate whether there is a difference in Chartis measurement outcomes between PS and general anesthesia.

Substance P and the neurokinin-1 (NK-1) receptor are implicated in chronic refractory cough pathophysiology. We assessed the efficacy and safety of orvepitant, a brain-penetrant NK-1 antagonist, in an open-label study in CRC patients with chronic refractory cough.

Several recent cases associating cleaned and high-level disinfected duodenoscopes with outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs) may cause bronchoscopists, pulmonologists, and other stakeholders to inquire about the effectiveness of today's practices for reprocessing flexible bronchoscopes. The primary objectives of this study were to address this question and investigate the risk of bronchoscopes transmitting infections of CRE and related MDROs. The published literature and the US Food and Drug Administration's medical device database of adverse events were searched beginning in 2012, when endoscopy first emerged as a recognized risk factor for transmission of CRE. The Internet was also searched during this same time frame to identify other relevant cases. Several cases associating reprocessed bronchoscopes with infections of CRE or a related MDRO were identified. This study's findings suggest that bronchoscopes may pose an underrecognized potential for transmission of CRE and related MDROs, warranting greater public awareness, enhanced preventive measures, and updated reprocessing guidance. This study's data also suggest that the cleaning and high-level disinfection of bronchoscopes performed in accordance with published guidelines and manufacturer instructions may not always be sufficiently effective to eliminate this risk. Several factors were identified that can adversely affect a bronchoscope's reprocessing and pose a risk of transmission of these multidrug-resistant bacteria, including use of a damaged or inadequately serviced bronchoscope, and formation of an inaccessible biofilm. Recommendations are provided to improve the safety of flexible bronchoscopes, including supplementing their reprocessing with an enhanced measure such as sterilization when warranted, and strict adherence to a periodic servicing and maintenance schedule consistent with the bronchoscope manufacturer's instructions.

Age has been implicated as a factor in the plateau of long-term survival after lung transplant.

Air travel is physically demanding and, because obesity is rising, physicians increasingly need to assess whether such patients can fly safely. Our aim was to compare the diagnostic accuracy of two routinely used exercise tests, 50-m walk test and 6-min walk test, and hypoxic challenge testing (HCT) in obese individuals. We further explored the diagnostic potential of perceived dyspnea as measured with the Borg scale because this is often recorded subsequent to walking tests.