Airway hysteresis in normal subjects and individuals with chronic airflow obstruction

Specific conductance (sGaw) was measured without prior pharmacological induction of bronchoconstriction before and 5-10 s after a total lung capacity (TLC) volume history in normal subjects and in individuals with chronic airflow obstruction (CAO); increased sGaw after inspiration to TLC was considered evidence of airway hysteresis. Lung elastic recoil [Pst(L)] was also measured before and after inspiration to TLC. In the normal subjects 1) prebronchodilator sGaw increased significantly, whereas Pst(L) decreased significantly after inspiration to TLC; 2) modulators of cyclooxygenase activity had no significant effects on sGaw responses to deep inspiration; and 3) airway hysteresis diminished after inhalation of atropine or metaproterenol. In the CAO group 1) prebronchodilator sGaw and Pst(L) decreased significantly after inspiration to TLC, and 2) bronchoconstriction after deep inspiration diminished after inhalation of atropine or metaproterenol. This study demonstrates that normal airways exhibit hysteresis even without alteration of resting airway tone and that airway hysteresis is impaired in CAO.     

Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training.

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 +/- 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 +/- 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of approximately 80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups (P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.     

Ventilatory and diaphragmatic EMG responses to negative-pressure ventilation in airflow obstruction

To assess the responses of patients with chronic obstructive lung disease (COLD) to negative-pressure ventilation (NPV), we studied eight naive patients with moderate to severe COLD before (control) and during NPV with "low" (-10-cmH2O) and "high" (-30-cmH2O) pressure swings in a Drinker tank respirator. Tidal volume (VT) and minute ventilation (VE) were recorded from a Respitrace and diaphragmatic electromyogram (DEMG) from a bipolar esophageal electrode. During short, 5-min runs of "low" and "high" NPV, VT did not change and VE increased in a borderline significant way at -30-cmH2O NPV. Peak integrated DEMG amplitude did not change with respect to control during short runs of NPV. However, when NPV was maintained for 20-60 min, a significant (though small, 20%) decrease in peak DEMG amplitude was observed with respect to control. By contrast, in a ninth patient habituated to NPV, the decrease in peak DEMG amplitude during a 5-min run of NPV was 60%. Significant increases in arterial PO2 (at -10- and -30-cmH2O NPV) and decreases in arterial PCO2 (at -30-cmH2O NPV) were found during NPV for the whole group of patients. One-to-one phase locking between the respirator and patients was the most common pattern of entrainment observed. However, 1:1 phase locking did not preclude the presence of dissociation between the two pacemakers. We conclude that short runs of NPV in naive patients do not result in changes in DEMG, as opposed to immediate and nearly complete cessation of inspiratory activity in trained patients.     

Forced expiration: a test for airflow obstruction in horses.

The purpose of this study was to assess whether our method of inducing forced expiration detects small airway obstruction in horses. Parameters derived from forced expiratory flow-volume (FEFV) curves were compared with lung mechanics data obtained during spontaneous breathing in nine healthy horses, in three after histamine challenge, and in two with chronic obstructive pulmonary disease (COPD) pre- and posttherapy with prednisone. Parameters measured in the healthy horses included forced vital capacity (FVC = 41.6 +/- 5.8 liters; means +/- SD) and forced expiratory flow (FEF) at various percentages of FVC (range of 20.4-29.7 l/s). Histamine challenge induced a dose-dependent decrease in FVC and FEF at low lung volume. After therapy, lung function of the two COPD horses improved to a point where one horse had normal lung mechanics during tidal breathing; however, FEF at 95% of FVC (4.9 l/s) was still decreased. We concluded that FEFV curve analysis allowed the detection of induced or naturally occurring airway obstruction.     

Response of pulmonary circulation to oral pirbuterol in chronic airflow obstruction.

The effects of the oral beta agonist pirbuterol on pulmonary haemodynamics and gas exchange were studied in nine patients with severe irreversible airflow obstruction and moderate arterial hypoxaemia. After administration of 15 mg pirbuterol pulmonary vascular resistance fell by 19% but cardiac output rose by 24%, so that pulmonary arterial pressure showed no significant change. Systemic arterial oxygen pressure fell by 7%, limiting the rise in oxygen delivery to 21%. All changes were significant at the 2% level. These results show that pirbuterol dilates the pulmonary bed at the cost of a slight worsening of gas exchange, which is compensated by an independent rise in blood flow.     

Vitamin E deficiency in the rat. IV. Alteration in mitochondrial membrane and its relation to respiratory decline

The respiratory control and rate of oxidation of exogenous NADH in vitro by liver mitochondria from vitamin E deficient rats were studied as a means of providing information concerning possible mitochondrial membrane alterations due to the deficiency.When mitochondria were aged at different temperatures for various periods of time, half-maximal inhibition of respiratory control occurred at lower temperatures and shorter aging periods in deficient mitochondria than in normal ones. Also, respiratory control was lost more rapidly in deficient mitochondria than in normal ones in the presence of either digitonin or low (hypotonic) concentrations of mannitol.Microsomes, both freshly prepared and boiled, dramatically lowered respiratory control and the effect was greater in the deficient mitochondria. Bovine serum albumin overcame the suppressed respiratory control, and exogenously added fatty acids mimiced the action of the microsomes.NADH oxidation by normal mitochondria proceeded slowly in isotonic media, while mitochondria of vitamin E deficient rats oxidized NADH much more rapidly. When mitochondria were subjected to ultrasonic disruption or incubated in hypotonic media, the rates of NADH oxidation by both types of mitochondria were similar.Respiratory decline associated with oxidation of β-hydroxybutyrate by the deficient mitochondria was decreased by including in the medium either a high concentration of NAD⁺, 0.5 mm oxalacetate, or 2 mm aspartate plus 1 mm α-ketoglutarate. This observation, plus the finding of similar activities of malate dehydrogenase and glutamic-oxalacetic transminase in normal and deficient livers, suggests that the action of each was due to an elevation of the mitochondrial NAD⁺/NADH ratio via a malate shuttle and cytoplasmic and mitochondrial glutamic-oxalacetate transaminase. It is postulated that the marked mitochondrial respiratory decline in the deficient rats is attributed to a limiting availability of NAD⁺ and a low ratio of NAD⁺ to NADH.     

Effect of substance P on cardiovascular and respiratory function in subjects

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.     

Lung function and breathing pattern in subjects developing high altitude pulmonary edema

Introduction

The purpose of the study was to comprehensively evaluate physiologic changes associated with development of high altitude pulmonary edema (HAPE). We tested whether changes in pulmonary function and breathing pattern would herald clinically overt HAPE at an early stage.

Methods

In 18 mountaineers, spirometry, diffusing capacity, nitrogen washout, nocturnal ventilation and pulse oximetry were recorded at 490 m and during 3 days after rapid ascent to 4559 m. Findings were compared among subjects developing HAPE and those remaining well (controls).

Results

In 8 subjects subsequently developing radiographically documented HAPE at 4559 m, median FVC declined to 82% of low altitude baseline while closing volume increased to 164% of baseline (P<0.05, both instances). In 10 controls, FVC decreased slightly (to 93% baseline, P<0.05) but significantly less than in subjects with HAPE and closing volume remained unchanged. Sniff nasal pressure was reduced in both subjects with and without subsequent HAPE. During nights at 4559 m, mean nocturnal oxygen saturation dropped to lower values while minute ventilation, the number of periodic breathing cycles and heart rate were higher (60%; 8.6 L/min; 97 cycles/h; 94 beats/min, respectively) in subjects subsequently developing HAPE than in controls (73%; 5.1 L/min; 48 cycles/h; 79 beats/min; P<0.05 vs. HAPE, all instances).

Conclusion

The results comprehensively represent the pattern of physiologic alterations that precede overt HAPE. The changes in lung function are consistent with reduced lung compliance and impaired gas exchange. Pronounced nocturnal hypoxemia, ventilatory control instability and sympathetic stimulation are further signs of subsequent overt HAPE.

Registration

ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00274430","term_id":"NCT00274430"}}NCT00274430     

Accelerated decline in lung function in smoking women with airway obstruction: SAPALDIA 2 cohort study

Background

The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women.

Methods

In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 – 60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years.

Results

In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV₁ was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV₁ was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002).

Conclusion

There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.     

Properties and function of the respiratory chain of freshwater mussel spermatozoa in relation to motility

1. The spermatozoa of the freshwater mussel (Hyriopsis schlegelii) contain cytochromes aa₃, b and c, flavoproteins and nicotinamide nucleotides in molar ratios of 1.0:0.9:1.8:1.8:8.7. Cytochrome c₁ is not detectable even at liquid-N₂ temperature, but a c₁-like cytochrome with an -band at 550 mμ is found at liquid-N₂ temperature in a cell preparation from which cytochrome c is completely removed.

2. The near-ultraviolet difference spectrum of whole cells reveals an absorption peak at 315 mμ with a shoulder around 350 mμ.

3. Both the endogenous respiration and motility of spermatozoa are completely blocked by 0.2 mM CN⁻ and by 0.2 μM antimycin A. 2,4-Dinitrophenol and pentachlorophenol completely inhibit motility at the maximal stimulation of respiration. Rotenone strongly inhibits NADH oxidase of spermatozoa, although it has no effect on the respiration of whole cells.

4. It is concluded that the motility of mussel spermatozoa is tightly coupled to respiration, and the respiratory chain phosphorylating process is the only energy-supplying system for motility.     

Ambrosia fungi in the insect-fungi symbiosis in relation to cork oak decline

Ambrosia fungi live associated with beetles (Scolytidae and Platypodidae) in host trees and act as a food source for the insects. The symbiotic relation is important to the colonizing strategies of host trees by beetles. Ambrosia fungi are dimorphic: they grow as ambrosial form and as mycelium. The fungi are highly specialized, adapted to a specific beetle and to the biotope where they both live. In addition other fungi have been found such as tree pathogenic fungi that may play a role in insects host colonization success. Saprophytic fungi are also present in insects galleries. These may decompose cellulose and/or be antagonistic to other less beneficial fungi. This paper summarizes the importance of ambrosia fungi and the interaction with insects and hosts. The possibility of the transport of pathogenic fungi by Platypus cylindrus to cork oak thus contributing for its decline is discussed.     

Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction

Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning.