Low-cost air quality portable sensors and their potential use in respiratory health.

Air pollution is an environmental risk for the general population and for patients with various diseases, particularly respiratory diseases. Little data are available on personal exposure, but the recent emergence of low-cost air quality sensors (LCSs) should enable a better understanding of the health impacts of air pollution at the individual level. However, the reliability and accuracy of most sensors in the market have not been established, and a thorough understanding of their strengths and limitations is needed. We therefore conducted a review to address the following questions: 1) What is an LCS and what is the extent of its possible application? 2) Is the data obtained a reliable indicator of exposure? 3) What are the advantages and disadvantages of LCSs? 4) Could LCSs be useful in investigating the impact of air pollution on respiratory health? Further studies are needed to promote the use of LCS in research settings and among respiratory patients. This will allow us to monitor exposure levels, provide alerts and study the respiratory effects of individual-level air pollution.

[Is hypoxia a factor in the progression of pulmonary sarcoidosis?] / L'hypoxie est-elle un facteur impactant l'évolution de la sarcoïdose pulmonaire ?

Sarcoidosis is a systemic granulomatous disease that can reduce life expectancy mainly due to pulmonary fibrosis resulting from granulomatous inflammation The lack of vascularization within pulmonary granulomas suggests that macrophages localized in the center of these structures are hypoxic. Hypoxia signaling pathways are known to be pro-inflammatory and pro-fibrotic in various pathological conditions. Recent data suggest an involvement of the transcription factor hypoxia-inducible factor (HIF) in the pathogenesis of sarcoidosis. This could represent a new research approach for the understanding and therapeutic management of sarcoidosis.

Enhanced sodium absorption in middle ear epithelial cells cultured at air-liquid interface.

CONCLUSION: As we demonstrated previously that transcription of alpha-ENaC was correlated with oxygen tension in the culture medium, this study suggests that the increase in alpha-ENaC expression observed under ALI conditions may result from greater oxygenation of ME cells. OBJECTIVE: The physiology of the middle ear (ME) is primarily concerned with keeping the cavities fluid-free, to allow transmission of sound vibrations from the eardrum to the inner ear. ME epithelial cells are thought to play a key role in this process as they actively absorb sodium and water in order to clear any excess fluid present in the cavities. MATERIAL AND METHODS: As an air-liquid interface (ALI) model has been shown to improve differentiation and enhance sodium absorption in other respiratory epithelia, we established an ALI model for ME cells. RESULTS: ME cells cultured under ALI conditions exhibited a fourfold increase in sodium absorption, which was not related to either a metabolic effect or to enhanced morphological differentiation, but instead to an increase in expression of the alpha-subunit of the epithelial sodium channel (alpha-ENaC).

Exacerbation of sleep-apnoea related nocturnal blood-pressure fluctuations in hypertensive subjects.

Obstructive sleep apnoea syndrome (OSAS) induces marked haemodynamic fluctuations during sleep that might be deleterious to the cardiovascular system. The influence of daytime blood pressure (BP) levels and aging on short-term BP variability during sleep in OSAS patients was investigated. Twenty-nine subjects with newly-diagnosed untreated OSAS were categorised into three groups: normotensive subjects aged <50 yrs (n=10); subjects aged <50 yrs with untreated hypertension (n=8); and normotensive subjects aged >50 yrs (n=11). Beat-by-beat BP was recorded with a Finapres device during polysomnography. The average values+/-SD of apnoea-related BP elevations and the values of the frequency distribution of all BP variations during sleep were assessed to estimate short-term BP variability. Apnoea-related systolic (or diastolic) BP elevations were significantly greater in hypertensives than in normotensives aged <50 yrs (50.3+/-4.88 versus 30.7+/-2.14 mmHg, p<0.001), as was the SD of systolic (or diastolic) BP variations during sleep (19.6+/-2.22 versus 11.1+/-0.73, p<0.001). Short-term BP variability was not significantly increased in normotensive elderly patients. To conclude, the results suggested that systemic hypertension is associated with a greater exacerbation of short-term variability during sleep in obstructive sleep apnoea syndrome patients.

Arterial blood gases during exercise: validity of transcutaneous measurements.

OBJECTIVE: To investigate the validity of transcutaneous measurements of blood gas tensions for the assessment of partial arterial pressure of oxygen (PaO(2)) and carbon dioxide (PaCO(2)) during treadmill exercise. DESIGN: Experimental, self-controlled against a reference standard. SETTING: Lung function laboratory. PATIENTS: Eighty-one patients with various lung diseases. INTERVENTIONS: At rest and at symptom-limited peak exercise, puncture of the radial artery with concurrent transcutaneous measures of blood gases. MAIN OUTCOME MEASURES: Arterial blood samples were analyzed with a radiometer to measure PaO(2) and PaCO(2). A microgas apparatus was used to measure gas tensions transcutaneously. Values obtained transcutaneously (TcPO(2), TcPCO(2)) were compared with those obtained by blood sample. TcPO(2) was adjusted as close as possible to the PaO(2) obtained in the same conditions, with the correction factor of the apparatus. Values obtained transcutaneously were compared with those obtained by blood sample to establish the sensitivity and specificity of the noninvasive method. RESULTS: Mean differences +/- standard deviation between transcutaneous and arterial tension at peak exercise were 0.4 +/- 7.0mmHg and 2.1 +/- 3.3mmHg for PaO(2) and PaCO(2), respectively. The transcutaneous device enabled us to predict a decrease in PaO(2) (>or=2mmHg) from rest to exercise with a sensitivity of 92.1% and a specificity of 90% and an increase in PaCO(2) with a sensitivity of 88% and a specificity of 58.9%. CONCLUSIONS: Although transcutaneous measurement are sufficiently sensitive and specific to detect patients whose PaO(2) decreases during exercise, its precision is not sufficient for gas exchange calculations.

Hypoxia increases glyceraldehyde-3-phosphate dehydrogenase transcription in rat alveolar epithelial cells.

Alveolar epithelial type II (ATII) cells are particularly hypoxia-tolerant in vitro. As one of the mechanisms of hypoxia tolerance is the induction of certain proteins, one of which is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we investigated whether hypoxia modified GAPDH expression in ATII cells. Hypoxia induced a time- and O(2) concentration-dependent accumulation of GAPDH mRNA in cultured rat ATII cells (2- to 3-fold the normoxic value after 18 h in 0% O(2)), an effect completely reversed by reoxygenation. GAPDH mRNA induction was accounted for by an increase in GAPDH gene transcription during hypoxia with no change in mRNA stability. GAPDH protein synthesis increased 3- to 4-fold after 18 h of 0% O(2), while the GAPDH protein steady-state level rose by 75%. GAPDH enzymatic activity in hypoxic cell homogenates increased by 45%. These results indicate that hypoxia induces GAPDH expression in ATII cells through an increase in transcription.

Hypoxia upregulates activity and expression of the glucose transporter GLUT1 in alveolar epithelial cells.

Alveolar epithelial cells (AEC) are directly exposed to high alveolar O(2) tension. Many pulmonary disorders are associated with a decrease in alveolar O(2) tension and AEC need to develop adaptative mechanisms to cope with O(2) deprivation. Under hypoxia, because of inhibition of oxidative phosphorylation, adenosine triphosphate supply is dependent on the ability of cells to increase anaerobic glycolysis. In this study we show that under hypoxia, primary rat AEC maintained their energy status close to that of normoxic cells through increasing anaerobic glycolysis. We therefore examined the effect of hypoxia on glucose transport and evaluated the mechanisms of this regulation. Hypoxia induced a stimulation of Na-independent glucose transport, as shown by the increase in 2-deoxy-D-glucose (DG) uptake. This increase was dependent on time and O(2) concentration: maximal at 0% O(2) for 18 h, and reversible after hypoxic cells were allowed to recover in normoxia. Concomitantly, exposure of AEC to hypoxia (18 h 0% O(2)) induced a 3-fold increase of glucose transporter GLUT1 at both protein and messenger RNA (mRNA) levels. To determine whether the increase in GLUT1 mRNA level was dependent on O(2) deprivation per se or resulted from decrease of oxidative phosphorylation, we examined in normoxic cells the effects of cobalt chloride and Na azide, respectively. Cobalt chloride (100 microM) and Na azide (1 mM) increased both mRNA levels and DG uptake, mimicking the effect of hypoxia. Electrophoretic mobility shift assays revealed a hypoxic and a cobalt chloride induction of a hypoxia-inducible factor (HIF) that bound to the sequence of nucleotides, corresponding to a hypoxia-inducible element upstream of the GLUT1 gene. AEC also expressed this factor under nonhypoxic conditions. Together, our results demonstrate that AEC increased glucose transport in response to hypoxia by regulating GLUT1 gene-encoding protein. This regulation likely occurred at the transcriptional level through the activation of an HIF, the nature of which remains to be elucidated.

Effect of celiprolol treatment in hypertensive patients with sleep apnea.

The effects of a beta-blocker, celiprolol, on sleep and arterial blood pressure (BP) were evaluated during a single-blind study in seven hypertensive patients with sleep apnea. Diurnal ambulatory BP measurements with an automatic cuff-inflation device and polysomnography with simultaneous Finapres BP recording were performed separately on consecutive days at the end of two 21-day treatment periods involving placebo followed by celiprolol (200 mg/day). Age was 59 +/- 2.5 yr (m +/- sem) and body mass index 33.2 +/- 2.3 kg. m-2. Diurnal ambulatory BP was significantly lower with celiprolol than with placebo (systolic 139 +/- 4 vs 152 +/- 5 mmHg, diastolic 86 +/- 2 vs 96 +/- 2 mmHg). The apnea-hypopnea index was similar under celiprolol and placebo (48 +/- 7.4 vs 53 +/- 7.8, respectively), as were the total sleep time and percent of duration of the different sleep stages. Individual average BP values were significantly lower during REM sleep under celiprolol but remained similar under celiprolol and placebo in the other sleep stages. Variability of nocturnal BP (assessed by the SD of distribution of BP variations) was not affected by celiprolol. In conclusion, celiprolol which decreased daytime BP, did not affect sleep pattern or respiratory disturbances, or nocturnal BP variability related to apnea.

Nasal resistance in snorers with or without sleep apnea: effect of posture and nasal ventilation with continuous positive airway pressure.

We investigated the effects of posture and nasal ventilation with continuous airway pressure (CPAP) on nasal resistance in snorers with or without obstructive sleep apnea (OSA). Posterior rhinomanometry was performed in 70 snorers referred for polysomnography and in 11 nonsnoring volunteers, (1) in the seated posture; (2) and (3) after 10 minutes in the supine position, before and after inhalation of oxymetazoline; and (4) 10 minutes after return to the seated position. The effect of CPAP on posterior rhinomanometry was also examined in the nonsnorers and in 12 of the snorers. Changing from the seated to the supine position resulted in an increase in resistance in snorers and nonsnorers (resistance supine 182 +/- 10.9% and 128 +/- 6.7% respectively of seated value, p < 0.05). After oxymetazoline instillation, resistance in the supine position decreased but remained higher in snorers than baseline value in the seated position. Effects of posture and oxymetazoline were similar in snorers with or without sleep apnea. During nasal ventilation with CPAP, resistance was 30 +/- 3.8 and 45 +/- 4.4% of value before CPAP in snorers and nonsnorers, respectively (p < 0.05). These effects of posture and CPAP were also observed when resistance was measured with anterior rhinomanometry. In conclusion, nasal resistance measured with posterior rhinomanometry in the supine position is not predictive for OSA. Nasal ventilation with CPAP resulted in an acute and marked decrease in nasal resistance.

Hypoxia downregulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells.

Decrease in alveolar oxygen tension may induce acute lung injury with pulmonary edema. We investigated whether, in alveolar epithelial cells, expression and activity of epithelial sodium (Na) channels and Na,K-adenosine triphosphatase, the major components of transepithelial Na transport, were regulated by hypoxia. Exposure of cultured rat alveolar cells to 3% and 0% O2 for 18 h reduced Na channel activity estimated by amiloride-sensitive 22Na influx by 32% and 67%, respectively, whereas 5% O2 was without effect. The decrease in Na channel activity induced by 0% O2 was time-dependent, significant at 3 h of exposure and maximal at 12 and 18 h. It was associated with a time-dependent decline in the amount of mRNAs encoding the alpha-, beta-, and gamma-subunits of the rat epithelial Na channel (rENaC) and with a 42% decrease in alpha-rENaC protein synthesis as evaluated by immunoprecipitation after 18 h of exposure. The 0% O2 hypoxia also caused a time-dependent decrease in (1) ouabain-sensitive 86Rubidium influx in intact cells, (2) the maximal velocity of Na,K-ATPase on crude homogenates, and (3) alpha1- and beta1-Na,K-ATPase mRNA levels. Levels of rENaC and alpha1-Na,K-ATPase mRNA returned to control values within 48 h of reoxygenation, and this was associated with complete functional recovery. We conclude that hypoxia induced a downregulation of expression and activity of epithelial Na channels and Na,K-ATPase in alveolar cells. Subsequent decrease in Na reabsorption by alveolar epithelium could participate in the maintenance of hypoxia-induced alveolar edema.

Rat lung alveolar type II cell line maintains sodium transport characteristics of primary culture.

Culture of primary alveolar type II cells has been widely used to investigate the Na+ transport characteristics of alveolar epithelium. However, this model was restricted by early morphological and physiological dedifferentiation in culture. Recently, a cell line has been obtained by transfection of neonatal type II cells with the simian virus SV40 large T antigen gene (SV40-T2). SV40-T2 cells have retained proliferative characteristics of the primary type II cells (Clement et al., 1991, Exp. Cell Res., 196:198-205.) In the present study, we have characterized Na+ transport pathways in SV40-T2 cells. SV40-T2 cells retained most cardinal properties of the original alveolar epithelial cells. Na+ entry occurred, as in primary cultures, through both Na(+)-cotransporters and amiloride-sensitive Na+ channels. SV40-T2 cells expressed Na(+)-phosphate. Na(+)-amino acid and Na(+)-K(+)-Cl cotransports which are quantitatively similar to that of primary cultures. The existence of amiloride-sensitive Na+ channels was supported by molecular and functional data. SV40-T2 expressed the cloned alpha- and gamma-mRNAs for the rat epithelial Na+ channel (rENaC), whereas beta subunit was not detected, and 22Na+ influx was significantly inhibited by 10 microM amiloride. Na+, which enters SV40-T2 cells, is extruded through a Na+, K(+)-ATPase: mRNA for alpha 1 and beta 1 isoforms of Na+, K(+)-ATPase were present and Na+, K(+)-ATPase activity was evidenced either on intact cells by the presence of a ouabain-sensitive component of 86Rb+ influx or on cell homogenates by the measurement of ouabain-inhibitable ATP hydrolysis. These results indicate that SV40-T2 cell line displays most of the Na+ transport characteristics of well-differentiated primary cells in the first days of culture. We conclude that the SV40-T2 cell line provides a model of differentiated alveolar type II cells and may be a powerful tool to study, in vitro, the modulation of Na+ transport in pathophysiological conditions.

Inhibition of Na-K-ATPase activity after prolonged hypoxia in an alveolar epithelial cell line.

Exposure to alveolar hypoxia may induce acute pulmonary edema. Because the vectorial sodium transport by alveolar epithelium represents an important mechanism for alveolar edema clearance, we examined whether hypoxia affects Na-K-ATPase activity in cultured SV40-transformed rat alveolar type II cells (SV40 ATII cells). Hypoxic exposures (O or 5% O2 for at least 12 h) induced a time- and O2 concentration-dependent decrease in ouabain-sensitive rubidium (osRb) influx. Neither the sensitivity of Rb influx to ouabain nor the maximum velocity of the enzyme measured on crude cell homogenates was affected by hypoxia. The osRb influx decrease was independent of hypoxia-induced ATP depletion. Na-K-ATPase inhibition was most likely related to impaired calcium homeostasis, because 1) calcium influx was increased in hypoxic cells, 2) hypoxia-induced osRb influx decrease was completely prevented by nifedipine (10-5 M), and 3) osRb influx decreased in normoxic cells incubated with ionomycin (10-6 M, 15 min). Furthermore, hypoxia-induced Na-K-ATPase impairment might be due, at least in part, to the endogenous release by hypoxic cells of a lipidic factor in extracellular medium, because incubation of normoxic cells with hypoxic cells conditioned medium (CM), or with the lipidic subphase from hypoxic cells CM, also induced a partial decrease in osRb influx. This decrease was associated with increased calcium influx into normoxic cells and was suppressed either by the removal of external calcium or by nifedipine, suggesting that the lipidic factor exerted its inhibitory action on Na-K-ATPase via an enhancement of calcium entry. These results indicate that prolonged hypoxic exposure impairs Na-K-ATPase activity in SV40 ATII cells and may therefore decrease the vectorial sodium transport by alveolar epithelium.

Ultrastructural alterations of the air-blood barrier in sarcoidosis and hypersensitivity pneumonitis and their relation to lung histopathology.

To evaluate the incidence of air-blood barrier lesions in the course of chronic interstitial lung diseases, we studied by electron microscopy open lung biopsy specimens from patients with sarcoidosis or chronic hypersensitivity pneumonitis, and compared the distribution of ultrastructural air-blood barrier lesions (including swelling or destruction of epithelial and endothelial cells, type II cell hyperplasia, and basement membrane disruption) with the type of histopathologic abnormalities present (including inflammation, inflammation and fibrosis, or fibrosis alone). Ultrastructural lesions of the air-blood barrier were frequently observed in sarcoidosis as well as hypersensitivity pneumonitis. Their nature and distribution were highly dependent on the histologic pattern of lung tissue in which they were present: epithelial and/or endothelial injury was more frequently observed in inflammatory areas (90 to 100% of all lung specimens displaying inflammation alone), whereas type II cell hyperplasia was mainly identified in fibrotic tissues (83 to 100% of all lung specimens displaying fibrosis alone). Strikingly, in lung tissue considered as normal by light microscopy, air-blood barrier was frequently found to be damaged (50 to 62% of apparently normal lung specimens), suggesting that alveolar lesions may constitute an early phenomenon in the course of pulmonary inflammatory processes. The air-blood barrier alterations observed in this study may provide an anatomic basis for the modifications of alveolar permeability described in pulmonary sarcoidosis and hypersensitivity pneumonitis.

Diffuse interstitial lung disease due to AA amyloidosis.

A man developed interstitial lung disease and nephrotic syndrome due to AA amyloidosis. There was no evidence of an underlying disease predisposing to amyloidosis.

[Obturation of curved canals: in vitro study of lateral compaction]. / Obturation des canaux courbes: étude in vitro du compactage latéral.

The instrumentation and filling of teeth with curved canals are always difficult, therefore, the current study indicates solutions to problems encountered while preparing curved canals. The gutta condensation techniques and their ability to seal curved canals are also discussed. This study uses endodontic simulators to show the incidence of protocols and instrumentation on the ability of the lateral condensation technique to fill curved canals. This study, also, evaluate the lateral condensation technique combined with the thermomechanical in filling curved canals.