Normal breathing for healthy humans is taken for granted; it occurs without conscious effort using ambient (1-atmosphere) pressure with 21% oxygen (O 2 ) concentration. The body automatically adjusts for stress, exercise, altitude, and mild disease by increasing the volume and frequency of breathing. Longer term adaptations for exercise and altitude include increases in red blood cell counts and higher concentrations of capillaries in muscle tissue. When more challenging external environmental conditions or pulmonary illnesses exceed the capability for these adaptations, the human system requires technology to maintain sufficient ventilation to preserve life. On the environmental side there are two conditions to be addressed: toxicity of the surrounding atmosphere and changes in external pressure and O 2 concentration. On the medical side, mechanisms for assisting breathing include O 2 supplementation at ambient pressure, positive pressure/flow without additional O 2 , or a combination of both. This overview describes the various technologies applied to maintaining a safe breathing environment. Topics for environmental intervention include filter-based and flowing air-supply masks for toxic environments (occupational and laboratory protection), and on-demand gas supply systems for firefighters, self-contained underwater breathing apparatus divers, and altitude (high performance aircraft, spacecraft) applications. The topics for medical intervention include nasal cannula, continuous positive airway pressure, and medical ventilators. The primary purpose of this article is to provide a basic understanding of normal human breathing and the adaptation of breathing in different environments using available technologies.
We searched MEDLINE, CINAHL, and Cochrane Library database for articles published between January 1990 and December 2012. The update of this clinical practice guideline is based on 237 clinical trials, 54 reviews, and 23 meta-analyses on blood gas analysis (BGA) and hemoximetry. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation scoring system. BGA and hemoximetry are recommended for evaluating a patient's ventilatory, acid-base, and/or oxygenation status. BGA and hemoximetry are suggested for evaluating a patient's response to therapeutic interventions. BGA and hemoximetry are recommended for monitoring severity and progression of documented cardiopulmonary disease processes. Hemoximetry is recommended to determine the impact of dyshemoglobins on oxygenation. Capillary BGA is not recommended to determine oxygenation status. Central venous BGA and hemoximetry are suggested to determine oxygen consumption in the setting of early goal-directed therapies. For the assessment of oxygenation, a peripheral venous P O 2 is not recommended as a substitute for an arterial blood measurement (P aO 2 ). It is not recommended to use venous P CO 2 and pH as a substitute for arterial blood measurement of P aCO 2 and pH. It is suggested that hemoximetry is used in the detection and evaluation of shunts during diagnostic cardiac catheterization.
Volatile organic compounds (VOCs) are byproducts from metabolic pathways that can be detected in exhaled breath and have been reported as biomarkers for different diseases. The gold standard for analysis is gas chromatography–mass spectrometry (GC–MS), which can be coupled with various sampling methods. The current study aims to develop and compare different methods for sampling and preconcentrating VOCs using solid-phase microextraction (SPME). An in-house sampling method, direct-breath SPME (DB–SPME), was developed to directly extract VOCs from breath using a SPME fiber. The method was optimized by exploring different SPME types, the overall exhalation volume, and breath fractionation. DB–SPME was quantitatively compared to two alternative methods involving the collection of breath in a Tedlar bag. In one method, VOCs were directly extracted from the Tedlar bag (Tedlar–SPME) and in the other, the VOCs were cryothermally transferred from the Tedlar bag to a headspace vial (cryotransfer). The methods were verified and quantitatively compared using breath samples (n = 15 for each method respectively) analyzed by GC–MS quadrupole time-of-flight (QTOF) for compounds including but not limited to acetone, isoprene, toluene, limonene, and pinene. The cryotransfer method was the most sensitive, demonstrating the strongest signal for the majority of the VOCs detected in the exhaled breath samples. However, VOCs with low molecular weights, including acetone and isoprene, were detected with the highest sensitivity using the Tedlar–SPME. On the other hand, the DB–SPME was less sensitive, although it was rapid and had the lowest background GC–MS signal. Overall, the three breath-sampling methods can detect a wide variety of VOCs in breath. The cryotransfer method may be optimal when collecting a large number of samples using Tedlar bags, as it allows the long-term storage of VOCs at low temperatures (−80 °C), while Tedlar–SPME may be more effective when targeting relatively small VOCs. The DB-SPME method may be the most efficient when more immediate analyses and results are required.
Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx), which in turn accelerate pulmonary function decline and decrease survival rate. An overarching challenge is that there is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant research priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other CF clinical factors, exhaled breath samples were collected from 18 subjects with CF, with some experiencing PEx and others serving as a baseline. Exhaled breath was collected in Tedlar bags during tidal breathing and cryotransferred to headspace vials for VOC analysis by solid phase microextraction coupled to gas chromatography–mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator treatment (HEMT), and the need for inhaled tobramycin) were also explored. Two volatile aldehydes (octanal and nonanal) were upregulated in patients not taking the HEMT. VOCs correlating to potential confounding variables were removed and then analyzed by regression for significant correlations with FEV1pp measurements. Interestingly, the VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowest p-value when comparing subjects at baseline and during PEx. Other VOCs that were differentially expressed due to PEx that were identified in this study include durene, 2,4,4-trimethyl-1,3-pentanediol 1-isobutyrate and 5-methyltridecane. Receiver operator characteristic curves were developed and showed 3,7-dimethyldecane had higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that VOCs in exhaled breath may be a rich source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.