Rationale

Infant pulmonary function testing (IPFT) has become an important clinical tool for the evaluation of lung function in infants with Cystic Fibrosis (CF); however, it is still unclear whether lung function in infancy is predictive of lung function later in life. We hypothesized that measures of airflow obstruction by IPFT would correlate strongly with lung function by conventional spirometry later in childhood.



Study Design and Methodology

A retrospective analysis was performed of all CF infants studied with IPFT at the University of Minnesota Children's Hospital between September 1994 and March 2003. A total of 41 patients underwent IPFT and had valid spirometry results available at age 6 or later. IPFT values, such as I:E ratio, respiratory rate, tidal volume, and Tptef/Te, were calculated from tidal breathing loops. Passive respiratory system mechanics, which included Crs, Rrs, and τrs, were measured by the single breath end-inspiratory occlusion technique. Forced expiratory flows, including VmaxFRC, FVC, FEF50, and FEF75, were obtained by rapid thoracic compression and included a full vital capacity maneuver by the multiple inflation method. FRC measurements were calculated from data obtained via nitrogen washout in a subset of patients. In addition, information on age at diagnosis and results of oropharyngeal (OP) cultures at diagnosis and on subsequent visits was recorded. Standard spirometry was performed in all patients starting at age 5. The first valid flow-volume loop after age six was selected for analysis.



Results

Significant correlations were observed for the Rrs and the FEF50 by IPFT and the FEV1 and the FEF25–75 by standard spirometry (r > 0.4 and P < 0.03 for all correlations). These correlations were the strongest for those IPFT measurements obtained within 1 month of diagnosis and when Rrs was expressed as sGrs. The correlations observed were independent of the effects of age at diagnosis, gender and presence of Pseudomonas in oropharyngeal cultures at the time of diagnosis. Mean Rrs declined from 0.050 to 0.027 cm H2O/ml/sec with treatment (P < 0.0001). There were no other significant associations found between other IPFT values measured and FEV1 by spirometry.



Conclusions

Measures of airflow obstruction on IPFT, specifically Rrs, sGrs, and FEF50, were strongly correlated with future lung function. IPFT measurement of Rrs in addition to forced expiratory flows may help select patients at the greatest risk of early lung function decline. This study supports the use of Rrs as a surrogate variable to help assess the impact of early therapies in CF. Pediatr Pulmonol. 2009; 44:330–339. © 2009 Wiley-Liss, Inc.

Longitudinal assessment of lung function from infancy to childhood in patients with cystic fibrosis

In a previous study, exhaled carbon monoxide (eCO) has been assessed in healthy non-smokers with a photo acoustic spectrometer Bruel&Kjaer 1312. Unexpectedly, values were higher than those reported in literature, which were mostly obtained with electrochemical analysers. This study was aimed to compare eCO values obtained with Bruel&Kjaer 1312 and PiCO + Smokerlyzer, a largely utilized electrochemical analyser. Thirty-four healthy subjects, 15 non-smokers and 19 smokers, underwent eCO assessment with Bruel&Kjaer 1312 and PiCO + Smokerlyzer during a prolonged expiration (15 seconds). Bruel&Kjaer 1312 assessed CO concentration 7 and 12 seconds after the beginning of expiration and displayed the mean value. PiCO + Smokerlyzer was utilized according to the manufacturer’s recommendations. In vitro, the two devices were tested with standard concentrations of CO in nitrogen (5, 9.9, 20, and 50 ppm), and the time needed by PiCO + Smokerlyzer readings to stabilize was assessed at different gas flows. Both Bruel&Kjaer 1312 and PiCO + Smokerlyzer presented very good internal consistency. The values provided were strictly correlated, but at low test concentrations, the Bruel&Kjaer 1312 readings were greater than the PiCO + Smokerlyzer, and vice versa. PiCO + Smokerlyzer overestimated the CO standard concentrations at 5 and 9.9 ppm by 20%, while Bruel&Kjaer 1312 measures were correct. PiCO + Smokerlyzer readings stabilized in 12 seconds during in vitro tests and in 15 seconds during in vivo measurements, suggesting that the values displayed corresponded to the initial phase of expiration. Differences between Bruel&Kjaer 1312 and PiCO + Smokerlyzer may be explained because Bruel&Kjaer 1312 measured CO levels in the middle and at the end of expiration while PiCO + Smokerlyzer assessed them in the initial part of expiration.

/pdf/normal-values-of-exhaled-carbon-monoxide-in-healthy-subjects-3t0h9go7y3.pdf

Normal values of exhaled carbon monoxide in healthy subjects: comparison between two methods of assessment.

To compare the effects of thoracic load carriage on the ventilatory and perceptual responses to graded exercise, 14 pairs of height-matched, physically active males and females completed randomly ordered modified Balke treadmill exercise tests with and without a correctly sized and fitted 20.4 kg backpack and work clothing. Subjects walked at 1.56 m.s− 1 while grade was increased by 2% every 2 min until exhaustion. Ventilatory responses were measured with open circuit spirometry and perceptual responses were evaluated using the modified Borg scale. Inspiratory capacity maneuvers were performed to calculate operating lung volumes. Despite height matching, males had significantly greater lung volumes and peak oxygen uptake (
 $$\dot {V}$$
 O2peak). Peak $$\dot {V}$$
 O2 and ventilation (
 $$\dot {V}$$
 E) were lower (p < 0.05) for all subjects under load. Throughout exercise, the ventilatory equivalents for $$\dot {V}$$
 O2 and carbon dioxide production were significantly higher in females, independent of condition. At similar relative submaximal intensities (%
 $$\dot {V}$$
 O2peak), there was no difference in $$\dot {V}$$
 E between conditions in either group, however, all subjects adopted a rapid and shallow breathing pattern under load with decreased tidal volume secondary to lower end-inspiratory lung volume. The relative changes in breathing pattern and operating lung volume between unloaded and loaded conditions were similar between males and females. Females reported significantly higher dyspnea ratings for a given $$\dot {V}$$
 E compared to males; however, the relationship between dyspnea and $$\dot {V}$$
 E was unaffected by load carriage. The relative response patterns for ventilatory and perceptual responses to graded exercise with thoracic loading were similar in males and females.

Ventilatory responses in males and females during graded exercise with and without thoracic load carriage.

/pdf/breathing-s-training-and-the-pelvic-floor-a-basic-concept-2k924gdw.pdf

Breathing, (S)Training and the Pelvic Floor—A Basic Concept

Mechanical biomarkers distinguish health conditions through quantitative mechanical measurements. The emergence and establishment of nanotechnology in the last decades have provided new tools to obtain mechanical biomarkers at the nanoscale. Mechanical measurements are reproducible, label‐free, start to be applied in vivo can be high throughput, and require small samples. Mechanical protocols in clinical practice at the macro scale like palpation or blood pressure measurement are routinely used by medical doctors. Nanotechnology brought mechanical sensing to the next scale, where cells, tissues, and proteins can be probed and linked to medical conditions. Mechanical changes in cells and tissues may be detected before other markers, such as protein expression, providing an important advantage as biomarkers. In the present review, we explore the biomarker's historical evolution, describe mechanical biomarkers on various diseases and novel discoveries in the nanomechanical field for their characterization. We conclude that mechanical biomarkers are establishing novel hallmarks in diseases, in several cases for early diagnostics of diseases and discovery of drug targets in the proteins involved in the mechanical changes, while advances in instrumentation are bringing commercial products into the clinical practice. Mechanical biomarkers along with clinical testing are establishing an important niche in the market, whose demand is increasing due to the expansion of personalized medicine and unmet needs in the clinics.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmr.3022

Advances in mechanical biomarkers

The ARDS is a clinical entity which from a mechanical point of view is characterized not only by a low respiratory compliance but also by a high respiratory resistance (R). In five ARDS patients we analyzed the changes in total R of the respiratory system (Rmax) and airway plus endotracheal tube R (Rmin) induced by changing the airflow (V) rate at constant tidal volume (VT) and total PEEP (PEEP plus autoPEEP). Patients were ventilated in volume controlled mode (VC) and VC with inverse ratio (VCIRV), both with constant insufflation flow. Signals of V, and airway pressure (Paw) were digitized (sampling frequency 200Hz) and acquired by an IBM 55SX computer in order to perform the following calculations: Rmax, Rmin, DR (Rmax-Rmin), static compliance (C). VT was obtained by digital integration of V. Rmin was corrected for the closing time of the inspiratory valve. Statistical analysis was performed with a two-way ANOVA. Results: V PEEPt Ti/Tt VT L/e cmH20 8 reL VC .76±.06 9.5±.4 34+.5 590±42 VCIRV .30+.02 8.4+.5 73+2 610±47 P= <.001 .15 <.001 .5

/pdf/respiratory-mechanics-i-1n33wo9c03.pdf

Respiratory mechanics I

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Respiratory mechanics I