Lung function is inextricably linked to mechanics. On short timescales every breath generates dynamic cycles of cell and matrix stretch, along with convection of fluids in the airways and vasculature. Perturbations such airway smooth muscle shortening or surfactant dysfunction rapidly alter respiratory mechanics, with profound influence on lung function. On longer timescales, lung development, maturation, and remodeling all strongly depend on cues from the mechanical environment. Thus mechanics has long played a central role in our developing understanding of lung biology and respiratory physiology. This concise review focuses on progress over the past five years in elucidating the molecular origins of lung mechanical behavior, and the cellular signaling events triggered by mechanical perturbations that contribute to lung development, homeostasis, and injury. Special emphasis is placed on the tools and approaches opening new avenues for investigation of lung behavior at integrative cellular and molecular scales. We conclude with a brief summary of selected opportunities and challenges that lie ahead for the lung mechanobiology research community.
mechanotransduction; extracellular matrix; respiratory; stretch
Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.
Changes in the shape of the lung during breathing determine the movement of airways and alveoli, and thus impact airflow dynamics. Modeling airflow dynamics in health and disease is a key goal for predictive multiscale models of respiration. Past efforts to model changes in lung shape during breathing have measured shape at multiple breath-holds. However, breath-holds do not capture hysteretic differences between inspiration and expiration resulting from the additional energy required for inspiration. Alternatively, imaging dynamically – without breath-holds – allows measurement of hysteretic differences. In this study, we acquire multiple micro-CT images per breath (4DCT) in live rats, and from these images we develop, for the first time, dynamic volume maps. These maps show changes in local volume across the entire lung throughout the breathing cycle and accurately predict the global pressure-volume (PV) hysteresis. Male Sprague-Dawley rats were given either a full- or partial-lung dose of elastase or saline as a control. After three weeks, 4DCT images of the mechanically ventilated rats under anesthesia were acquired dynamically over the breathing cycle (11 time points, ≤100 ms temporal resolution, 8 cmH2O peak pressure). Non-rigid image registration was applied to determine the deformation gradient – a numerical description of changes to lung shape – at each time point. The registration accuracy was evaluated by landmark identification. Of 67 landmarks, one was determined misregistered by all three observers, and 11 were determined misregistered by two observers. Volume change maps were calculated on a voxel-by-voxel basis at all time points using both the Jacobian of the deformation gradient and the inhaled air fraction. The calculated lung PV hysteresis agrees with pressure-volume curves measured by the ventilator. Volume maps in diseased rats show increased compliance and ventilation heterogeneity. Future predictive multiscale models of rodent respiration may leverage such volume maps as boundary conditions.
Inhalation of helium-oxygen (He/O2) mixtures has been explored as a means to lower the work of breathing of patients with obstructive lung disease. Non-invasive ventilation (NIV) with positive pressure support is also used for this purpose. The bench experiments presented herein were conducted in order to compare simulated patient inspiratory effort breathing He/O2 with that breathing medical air, with or without pressure support, across a range of adult, obstructive disease patterns.
Patient breathing was simulated using a dual-chamber mechanical test lung, with the breathing compartment connected to an ICU ventilator operated in NIV mode with medical air or He/O2 (78/22 or 65/35%). Parabolic or linear resistances were inserted at the inlet to the breathing chamber. Breathing chamber compliance was also varied. The inspiratory effort was assessed for the different gas mixtures, for three breathing patterns, with zero pressure support (simulating unassisted spontaneous breathing), and with varying levels of pressure support.
Inspiratory effort increased with increasing resistance and decreasing compliance. At a fixed resistance and compliance, inspiratory effort increased with increasing minute ventilation, and decreased with increasing pressure support. For parabolic resistors, inspiratory effort was lower for He/O2 mixtures than for air, whereas little difference was measured for nominally linear resistance. Relatively small differences in inspiratory effort were measured between the two He/O2 mixtures. Used in combination, reductions in inspiratory effort provided by He/O2 and pressure support were additive.
The reduction in inspiratory effort afforded by breathing He/O2 is strongly dependent on the severity and type of airway obstruction. Varying helium concentration between 78% and 65% has small impact on inspiratory effort, while combining He/O2 with pressure support provides an additive reduction in inspiratory effort. In addition, breathing He/O2 alone may provide an alternative to pressure support in circumstances where NIV is not available or poorly tolerated.
Helium; Oxygen; Heliox; Inspiratory effort; Work of breathing; Airway resistance; Lung compliance; Non-invasive ventilation; Pressure support
Rationale: The clinical pathology describing infants with chronic lung disease of infancy (CLDI) has been limited and obtained primarily from infants with severe lung disease, who either died or required lung biopsy. As lung tissue from clinically stable outpatients is not available, physiological measurements offer the potential to increase our understanding of the pulmonary pathophysiology of this disease.
Objectives: We hypothesized that if premature birth and the development of CLDI result in disruption of alveolar development, then infants and toddlers with CLDI would have a lower pulmonary diffusing capacity relative to their alveolar volume compared with full-term control subjects.
Methods: We measured pulmonary diffusing capacity and alveolar volume, using a single breath-hold maneuver at elevated lung volume. Subjects with chronic lung disease of infancy (23–29 wk of gestation; n = 39) were compared with full-term control subjects (n = 61) at corrected ages of 11.6 (4.8–17.0) and 13.6 (3.2–33) months, respectively.
Measurements and Main Results: Alveolar volume and pulmonary diffusing capacity increased with increasing body length for both groups. After adjusting for body length, subjects with CLDI had significantly lower pulmonary diffusing capacity (2.88 vs. 3.23 ml/min/mm Hg; P = 0.0004), but no difference in volume (545 vs. 555 ml; P = 0.58).
Conclusions: Infants and toddlers with CLDI have decreased pulmonary diffusing capacity, but normal alveolar volume. These physiological findings are consistent with the morphometric data obtained from subjects with severe lung disease, which suggests an impairment of alveolar development after very premature birth.
pulmonary diffusing capacity; alveolar volume; lung parenchyma; bronchopulmonary dysplasia
Breath analysis is a technique rapidly gaining ground as a non-invasive tool to diagnose and monitor various aspects of lung diseases. Measurement of exhaled breath is safe, rapid, simple to perform, and effort independent. Given that human breath contains upwards of 250 chemicals, the potential for developing new applications is high. Much of the current knowledge on breath analysis in respiratory medicine derives from years of experience gained in occupational settings, where breath analysis has been used to assess exposure to volatile chemicals. Laboratory based analysis of exhaled air is a complex, expensive and time consuming process and thus is not in wide spread use in occupational medicine. However, recent knowledge of exhaled breath analysis in pulmonology, in particular in bronchial asthma and lung cancer, and the development of fast, and easy to perform non-invasive procedures for breath analysis, re-opened possible application of exhaled breath as a novel approach for biological monitoring of inhaled pneumotoxic substances. The simultaneous quantification of biomarkers of dose and effect in exhaled air may provide new insights into lung damage occurring in workers exposed to inhaled toxicants, thus representing a new and fascinating application in risk assessment strategies.
exhaled breath; biomonitoring; biomarkers
Pulmonary disease changes the physiology of the lungs, which manifests as changes in respiratory mechanics. Therefore, measurement of respiratory mechanics allows a clinician to monitor closely the course of pulmonary disease. Here we review the principles of respiratory mechanics and their clinical applications. These principles include compliance, elastance, resistance, impedance, flow, and work of breathing. We discuss these principles in normal conditions and in disease states. As the severity of pulmonary disease increases, mechanical ventilation can become necessary. We discuss the use of pressure–volume curves in assisting with poorly compliant lungs while on mechanical ventilation. In addition, we discuss physiologic parameters that assist with ventilator weaning as the disease process abates.
In 1991, Frostell and colleagues reported that breathing low concentrations of nitric oxide (NO) decreased pulmonary artery pressure (PAP) in awake lambs with experimental pulmonary arterial hypertension (PAH) . Subsequently, efforts of multiple research groups studying animals and patients led to approval of inhaled NO by the US Food and Drug Administration in 1999 and the European Medicine Evaluation Agency and European Commission in 2001. Inhaled NO is currently indicated for the treatment of term and near-term neonates with hypoxemia and PAH. Since regulatory approval, several studies have suggested that NO inhalation can prevent chronic lung disease in premature infants. In addition, unanticipated systemic effects of inhaled NO may lead to treatments for a variety of disorders including ischemia-reperfusion injury.
This review summarizes the pharmacology and physiological effects of breathing NO. The application of inhaled NO to hypoxemic neonates with PAH is discussed including recent studies exploring the use of inhaled NO to prevent bronchopulmonary dysplasia in premature infants. This review also highlights the application of inhaled NO to treat adults with cardiopulmonary disease, strategies to augment the efficacy of inhaled NO, and potential applications of the systemic effects of the gas.
Breathing (especially deep breathing) antagonizes development and persistence of airflow obstruction during bronchoconstrictor stimulation. Force fluctuations imposed on contracted airway smooth muscle (ASM) in vitro result in its relengthening, a phenomenon called force fluctuation-induced relengthening (FFIR). Because breathing imposes similar force fluctuations on contracted ASM within intact lungs, FFIR represents a likely mechanism by which breathing antagonizes bronchoconstriction. While this bronchoprotective effect appears to be impaired in asthma, corticosteroid treatment can restore the ability of deep breaths to reverse artificially induced bronchoconstriction in asthmatic subjects. We previously demonstrated that FFIR is physiologically regulated through the p38 MAPK signaling pathway. While the beneficial effects of corticosteroids have been attributed to suppression of airway inflammation, we hypothesized that alternatively they might exert their action directly on ASM by augmenting FFIR as a result of inhibiting p38 MAPK signaling.
We tested this possibility in the present study by measuring relengthening in contracted canine tracheal smooth muscle (TSM) strips.
Our results indicate that dexamethasone treatment significantly augmented FFIR of contracted canine TSM. Canine tracheal ASM cells treated with dexamethasone demonstrated increased MAP kinase phosphatase (MKP)-1 expression and decreased p38 MAPK activity, as reflected in reduced phosphorylation of the p38 MAPK downstream target, HSP27.
These results suggest that corticosteroids may exert part of their therapeutic effect through direct action on ASM, by decreasing p38 MAPK activity and thus increasing FFIR.
asthma; bronchoprotection; bronchoconstriction; deep breaths; steroids; tidal breathing
In the early phase of their disease process, patients with acute lung injury are often ventilated with strategies that control the tidal volume or airway pressure, while modes employing spontaneous breathing are applied later to wean the patient from the ventilator. Spontaneous breathing modes may integrate intrinsic feedback mechanisms that should help prevent ventilator-induced lung injury, and should improve synchrony between the ventilator and the patient's demand. Airway pressure release ventilation with spontaneous breathing was shown to decrease cyclic collapse/recruitment of dependent, juxtadiaphragmatic lung areas compared with airway pressure release ventilation without spontaneous breathing. Combined with previous data demonstrating improved cardiorespiratory variables, airway pressure release ventilation with spontaneous breathing may turn out to be a less injurious ventilatory strategy.
BACKGROUND--Sighing breathing is observed in subjects suffering from anxiety with no apparent organic disease. METHODS--Lung volumes and expiratory flow rates were measured in 12 patients with a sighing pattern of breathing and in 10 normal subjects matched for age, gender, and anthropometric data. In both groups the measurements were made by spirographic and plethysmographic techniques. In normal subjects functional residual capacity (FRC) and residual volume (RV) were measured during normal breathing and again during simulated sighing breathing to exclude technical artifacts resulting from hyperventilation during measurement by the helium closed circuit method. RESULTS--Patients with a sighing pattern of breathing had a normal total lung capacity (TLC) but significantly different partitioning of lung compartments compared with normal subjects. The vital capacity (VC) was lower when measured by both spirographic and plethysmographic methods and RV was higher. The forced expiratory volume in one second (FEV1) was also lower in patients with sighing breathing. The FEV1/VC and the maximal expiratory flow rates at 50% and at 25% of the forced vital capacity (V50 and V25) were normal and similar in both groups. In normal subjects there were no differences in RV when measured during quiet or simulated sighing breathing. CONCLUSIONS--Subjects with sighing breathing have a normal TLC with a higher RV and lower VC than normal subjects. There was no obvious physiological or anatomical explanation for this pattern.
The diagnostic value of tidal breathing (TB) measurements in infants is controversially discussed. The aim of this study was to investigate to what extent the breathing pattern of sleeping infants with chronic lung diseases (CLD) differ from healthy controls with the same postconceptional age and to assess the predictive value of TB parameters.
In the age of 36–42 postconceptional weeks TB measurements were performed in 48 healthy newborns (median age and weight 7d, 3100 g) and 48 infants with CLD (80d, 2465 g)) using the deadspace-free flow-through technique. Once the infants had adapted to the mask and were sleeping quietly and breathing regularly, 20–60 breathing cycles were evaluated. Beside the shape of the tidal breathing flow-volume loop (TBFVL) 18 TB parameters were analyzed using ANOVA with Bonferroni correction. Receiver-operator characteristic (ROC) curves were calculated to investigate the discriminative ability of TB parameters.
The incidence of concave expiratory limbs in CLD infants was 31% and significantly higher compared to controls (2%) (p < 0.001). Significant differences between CLD infants and controls were found in 11/18 TB parameters. The largest differences were seen in the mean (SD) inspiratory time 0.45(0.11)s vs. 0.65(0.14)s (p < 0.0001) and respiratory rate (RR) 55.4(14.2)/min vs. 39.2(8.6)/min (p < 0.0001) without statistically significant difference in the discriminative power between both time parameters. Most flow parameters were strongly correlated with RR so that there is no additional diagnostic value. No significant differences were found in the tidal volume and commonly used TB parameters describing the expiratory flow profile.
The breathing pattern of CLD infants differs significantly from that of healthy controls. Concave TBFVL and an increased RR measured during quiet sleep and under standardized conditions may indicate diminished respiratory functions in CLD infants whereas most of the commonly used TB parameters are poorly predictive.
Ventilator-induced lung injury (VILI), one of the most serious complications of mechanical ventilation (MV), can impact patients' clinical prognoses. Compared to control ventilation, preserving spontaneous breathing can improve many physiological features in ventilated patients, such as gas distribution, cardiac performance, and ventilation-perfusion matching. However, the effect of spontaneous breathing on VILI is unknown. The goal of this study was to compare the effects of spontaneous breathing and control ventilation on lung injury in mechanically-ventilated healthy rabbits.
Sixteen healthy New Zealand white rabbits were randomly placed into a spontaneous breathing group (SB Group) and a control ventilation group (CV Group). Both groups were ventilated for eight hours using biphasic positive airway pressure (BIPAP) with similar ventilator parameters: inspiration pressure (PI) resulting in a tidal volume (VT) of 10 to 15 ml/kg, inspiratory-to-expiratory ratio of 1:1, positive end-expiration pressure (PEEP) of 2 cmH2O, and FiO2 of 0.5. Inflammatory markers in blood serum, lung homogenates and bronchoalveolar lavage fluid (BALF), total protein levels in BALF, mRNA expressions of selected cytokines in lung tissue, and lung injury histopathology scores were determined.
Animals remained hemodynamically stable throughout the entire experiment. After eight hours of MV, compared to the CV Group, the SB Group had lower PaCO2 values and ratios of dead space to tidal volume, and higher lung compliance. The levels of cytokines in blood serum and BALF in both groups were similar, but spontaneous breathing led to significantly lower cytokine mRNA expressions in lung tissues and lower lung injury histological scores.
Preserving spontaneous breathing can not only improve ventilatory function, but can also attenuate selected markers of VILI in the mechanically-ventilated healthy lung.
This minireview describes the health effects of antimony exposure in the workplace and the environment.
To collate information on the consequences of occupational and environmental exposure to antimony on physiological function and well-being.
The criteria used in the current minireview for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust.
The proportion of utilised and non-utilised articles was tabulated. Antimony toxicity is dependent on the exposure dose, duration, route (breathing, eating, drinking, or skin contact), other chemical exposures, age, sex, nutritional status, family traits, life style, and state of health. Chronic exposure to antimony in the air at levels of 9 mg/m3 may exacerbate irritation of the eyes, skin, and lungs. Long-term inhalation of antimony can potentiate pneumoconiosis, altered electrocardiograms, stomach pain, diarrhea, vomiting, and stomach ulcers, results which were confirmed in laboratory animals. Although there were investigations of the effect of antimony in sudden infant death syndrome, current findings suggest no link. Antimony trioxide exposure is predominant in smelters. Mining and exposure via glass working, soldering, and brazing are also important.
Antimony has some useful but undoubtedly harmful effects on health and well-being and measures need to be taken to prevent hazardous exposure of the like. Its biological monitoring in the workplace is essential.
Antimony; environment; exposure; health; occupation
Clinical and physiological studies were carried out in five patients with pneumatosis coli in order to investigate the origin of the high fasting breath hydrogen concentration in this condition and to determine its possible significance in the pathogenesis of the disease. All five patients excreted abnormally high fasting concentrations of hydrogen in their breath (69 +/- 9 ppm, mean +/- SEM). Moreover, analysis of the contents of the gas filled cysts revealed between 2% and 8% of hydrogen gas. Colonic washout significantly reduced breath hydrogen concentrations to 9 +/- 6 ppm, but did not abolish the cysts. Conversely, deflation of the cysts was achieved with oxygen or antibiotics, though this only reduced breath hydrogen concentrations to about 66% of their original value. After feeding a radiolabelled meal, breath hydrogen concentrations rose before the meal appeared to reach the colon, suggesting overgrowth of anaerobic bacteria in the small intestine. Despite this, 14C glycocholate breath tests were within normal limits. An alternative possibility is that the high levels of hydrogen excreted in the breath may be produced in the intestinal lumen possibly from the fermentation of copious amounts of colonic mucus. Finally, measurement of whole gut transit time and stool weight suggested that patients were constipated despite passing mucus and blood. The relevance of our observations to the pathogenesis of submucosal cysts is unclear, but the data favour the hypothesis that these are produced by invasion of the colonic submucosa with anaerobic bacteria.
Exhaled breath studies suggest that humans exhale fine particles during tidal breathing, but little is known of their physical origin in the respiratory system during health or disease.
Particles generated by 3 healthy and 16 human rhinovirus (HRV)-infected subjects were counted using an optical particle counter with nominal diameter-size bins ranging between 0.3 and 10 μm. Data were collected from HRV-infected subjects during tidal breathing. In addition, data from healthy subjects were collected during coughs, swallows, tidal breathing, and breathing to total lung capacity (TLC) and residual volume (RV). Using general additive models, we graphed exhaled particle concentration versus airflow during exhalation. Exhaled particles were collected from expired air on gelatin filters and analyzed for HRV via quantitative PCR.
HRV-infected subjects exhaled from 0.1 to 7200 particles per liter of exhaled air during tidal breathing (geometric mean = 32 part/L). A small fraction (24%) of subjects exhaled most (81%) of the particles measured and 82% of particles detected were 0.300–0.499 μm. Minute ventilation, maximum airflow during exhalation, and forced expiratory volume 1 second (FEV1 % predicted) were positively correlated with particle production. No human rhinovirus was detected in exhaled breath samples. Three healthy subjects exhaled less than 100 particles per liter of exhaled air during tidal breathing and increased particle concentrations more with exhalation to RV than with coughing, swallowing, or rapid exhalation.
Submicron particles were detected in the exhaled breath of healthy and HRV-infected subjects. Particle concentrations were correlated with airflow during the first half of exhalation, and peaked at the end of exhalation, indicating both lower and upper airways as particle sources. The effect of breathing maneuver suggested a major contribution from lower airways, probably the result of opening collapsed small airways and alveoli.
exhaled breath; aerosols; particles; human rhinovirus
Chronic obstructive pulmonary disease (COPD) is a condition in which there is limited airflow during expiration (exhaling, or breathing out) that is not fully reversible and usually worsens over time. The disease is estimated to kill more than 100,000 Americans each year, and costs related to care of patients with COPD are significant. Physiologically, COPD represents a disruption in ventilation and in the exchange of gases in the lungs. Laboratory tests indicate elevated CO2 levels, gradual reduction of the levels of oxygen and pH in arterial blood, and a consequent rise in the dead space fraction (DSF) of the lungs.
Patients with COPD exacerbation represent a large portion of those artificially ventilated. In an attempt to develop a prognostic tool for length of treatment, we compared the proportion of DSF to the length of mechanical ventilation (MV).
This study included 73 patients admitted to the intensive care unit (ICU) where they received MV due to exacerbation of COPD. Each patient’s arterial blood gases (ABG) were measured upon admission. PeCO2 was tested using a Datex S/5 instrument. Subsequently, DSF was calculated using the Bohr equation. Statistical data was analyzed using SPSS software.
Patients included in the study were ventilated from 6 to 160 hours (average 40 ± 47). In addition to ABG measurements, PeCO2 (expired CO2) levels were measured and DSF calculated for each patient. DSF values varied from 0.21 to 0.76 (average 0.119 ± 0.489). No correlation was found between DSF and length of artificial ventilation.
Evaluation of DSF does not provide a factor in estimating the length of treatment for patients with acute respiratory failure due to COPD exacerbation.
dead space; weaning; mechanical ventilation; COPD
The primary functional abnormality in asthma is airway hyperresponsiveness (AHR)—excessive airway narrowing to bronchoconstrictor stimuli. Our understanding of the underlying mechanism(s) producing AHR is incomplete. While structure-function relationships have been evoked to explain AHR (e.g., increased airway smooth muscle (ASM) mass in asthma) more recently there has been a focus on how the dynamic mechanical environment of the lung impacts airway responsiveness in health and disease. The effects of breathing movements such as deep inspiration reveal innate protective mechanisms in healthy individuals that are likely mediated by dynamic ASM stretch but which may be impaired in asthmatic patients and thereby facilitate AHR. This perspective considers the evidence for and against a role of dynamic ASM stretch in limiting the capacity of airways to narrow excessively. We propose that lung function measured after bronchial provocation in the laboratory and changes in lung function perceived by the patient in everyday life may be quite different in their dependence on dynamic ASM stretch.
Prediction equations have been evolved for the assessment of vital capacity, total lung capacity, and the single breath carbon monoxide transfer factor in haemoglobin SS and haemoglobin SC disease. These relationships take account of the growth disorder and anaemia in the sickle-cell states. The results suggest that, in the clinically stable state, any effects of alveolar capillary sickling and haemoconcentration and any altered reactivity of haemoglobins S and C with the test gas are of no significance for clinical respiratory physiology. Sex differences in lung function appear independent of haemoglobin type.
In chronic obstructive lung disease (asthma, chronic bronchitis, obstructive emphysema) there is a segmental reduction in the caliber of the airways, which always results in obstruction to air-flow. Increased airway resistance is a physiological expression of airway obstruction.
The addition of inspiratory flow rate control to an intermittent positive pressure breathing device permits slow filling of a lung with obstructed airways, and is presented as a simple means of reducing the high pulmonary flow resistance and increasing the tidal volume.
We develop optimal respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system. Specifically, we use classical calculus of variations minimization techniques to derive an optimal airflow pattern for inspiratory and expiratory breathing cycles. The physiological interpretation of the optimality criteria used involves the minimization of work of breathing and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase. Finally, we numerically integrate the resulting nonlinear two-point boundary value problems to determine the optimal airflow patterns over the inspiratory and expiratory breathing cycles.
[The operation and regulation of the lungs and the heart are closely related. This is evident when examining the anatomy within the thorax cavity, in the brainstem and in the aortic and carotid arteries where chemoreceptors and baroreceptors, which provide feedback affecting the regulation of both organs, are concentrated. This is also evident in phenomena such as respiratory sinus arrhythmia where the heart rate increases during inspiration and decreases during expiration, in other types of synchronization between the heart and the lungs known as cardioventilatory coupling and in the association between heart failure and sleep apnea where breathing is interrupted periodically by periods of no-breathing. The full implication and physiological significance of the cardio-respiratory coupling under normal, pathological or extreme physiological conditions are still unknown and are subject to ongoing investigation both experimentally and theoretically using mathematical models. This paper reviews mathematical models that take heart-lung interactions into account. The main ideas behind low dimensional, phenomenological models for the study of the heart-lung synchronization and sleep apnea are described first. Higher dimensions, physiology-based models are described next. These models can vary widely in detail and scope and are characterized by the way the heart-lung interaction is taken into account: via gas exchange, via the central nervous system, via the mechanical interactions and via time delays. The paper emphasizes the need for the integration of the different sources of heart-lung coupling as well as the different mathematical approaches.]
Background: Commercial aircraft cabins provide a hostile environment for patients with underlying respiratory disease. Although there are algorithms and guidelines for predicting in-flight hypoxaemia, these relate to chronic obstructive pulmonary disease (COPD) and data for interstitial lung disease (ILD) are lacking. The purpose of this study was to evaluate the effect of simulated cabin altitude on subjects with ILD at rest and during a limited walking task.
Methods: Fifteen subjects with ILD and 10 subjects with COPD were recruited. All subjects had resting arterial oxygen pressure (PaO2) of >9.3 kPa. Subjects breathed a hypoxic gas mixture containing 15% oxygen with balance nitrogen for 20 minutes at rest followed by a 50 metre walking task. Pulse oximetry (SpO2) was monitored continuously with testing terminated if levels fell below 80%. Arterial blood gas tensions were taken on room air at rest and after the resting and exercise phases of breathing the gas mixture.
Results: In both groups there was a statistically significant decrease in arterial oxygen saturation (SaO2) and PaO2 from room air to 15% oxygen at rest and from 15% oxygen at rest to the completion of the walking task. The ILD group differed significantly from the COPD group in resting 15% oxygen SaO2, PaO2, and room air pH. Means for both groups fell below recommended levels at both resting and when walking on 15% oxygen.
Conclusion: Even in the presence of acceptable arterial blood gas tensions at sea level, subjects with both ILD and COPD fall below recommended levels of oxygenation when cabin altitude is simulated. This is exacerbated by minimal exercise. Resting sea level arterial blood gas tensions are similarly poor in both COPD and ILD for predicting the response to simulated cabin altitude.
The pattern of volatile organic compounds (VOCs) in the exhaled breath of patients with lung cancer may be unique. New sensor systems that detect patterns of VOCs have been developed. One of these sensor systems, a colorimetric sensor array, has 36 spots composed of different chemically sensitive compounds impregnated on a disposable cartridge. The colours of these spots change based on the chemicals with which they come into contact. In this proof of principle study, the ability of this sensor system to detect a pattern of VOCs unique to lung cancer is assessed.
Individuals with lung cancer, those with other lung diseases and healthy controls performed tidal breathing of room air for 12 min while exhaling into a device designed to draw their breath across a colorimetric sensor array. The colour changes that occurred for each individual were converted into a numerical vector. The vectors were analysed statistically, using a random forests technique, to determine whether lung cancer could be predicted from the responses of the sensor.
143 individuals participated in the study: 49 with non‐small cell lung cancer, 18 with chronic obstructive pulmonary disease 15 with idiopathic pulmonary fibrosis 20 with pulmonary arterial hypertension 20 with sarcoidosis and 21 controls. A prediction model was developed using observations from 70% of the subjects. This model was able to predict the presence of lung cancer in the remaining 30% of subjects with a sensitivity of 73.3% and a specificity of 72.4% (p = 0.01).
The unique chemical signature of the breath of patients with lung cancer can be detected with moderate accuracy by a colorimetric sensor array.
Breath analysis is a powerful noninvasive technique for the diagnosis and monitoring of respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Nitric oxide (NO) and carbon monoxide (CO) are markers of airway inflammation and can indicate the extent of respiratory diseases. We have developed a compact fast response laser system for analysis of multiple gases by infrared absorption. The instrument uses room temperature quantum cascade lasers to simultaneously measure NO, CO, carbon dioxide (CO2) and nitrous oxide (N2O) in exhaled breath. Four breath flow rates are employed to explore their exchange dynamics in the lungs and airways. We obtain 1-s detection precisions of 0.5-0.8 parts-per-billion (ppb) for NO, CO, and N2O with an instrument response time of less than 1 s. The breath analysis system has been demonstrated in a preliminary study of volunteers. It is currently deployed in a trial clinical study.
Infrared spectroscopy; nitric oxide; quantum cascade laser