Sleep disordered breathing and nocturnal hypoxemia are very prevalent in a lung cancer screening population and may condition lung cancer screening findings: results of the prospective Sleep Apnea In Lung Cancer Screening (SAILS) study.

OBJECTIVE: Obstructive sleep apnea (OSA) can influence the appearance and proliferation of some tumors. The Sleep Apnea In Lung Cancer Screening (SAILS) study (NCT02764866) evaluated the prevalence of OSA and nocturnal hypoxemia in a high-risk population enrolled in a lung cancer screening program. METHODS: This was a prospective study of the prevalence of OSA in a lung cancer screening program. Subjects met the National Lung Screening Trial (NLST) age and smoking criteria (age 55-75 years; pack-years >30). Participants in the study were offered annual screening with low-dose computed tomography (LDCT) and pulmonary function testing, as well as home sleep apnea testing (HSAT) and a sleep-specific questionnaire. Sleep study-related variables, symptoms, and epidemiologic data were recorded. RESULTS: HSAT was offered to 279 subjects enrolled in our lung cancer screening program. HSAT results were available for 236 participants (mean age 63.6 years; mean tobacco exposure: 45 pack-years), of whom 59% were male and 53% were active smokers. Emphysema (74%) and chronic obstructive pulmonary disease (COPD) (62%) were common and in most cases mild in severity. OSA, including moderate to severe disease, was very common in this patient population. AHI distributions were as follows: AHI <5 (22.5%); 5-15 (36.4%); 15-30 (23.3%); and >30 (17.8%). Nocturnal hypoxemia (T90) (p = 0.003), diffusing capacity for carbon monoxide (DLCO) (p = 0.01), tobacco exposure (p = 0.024), and COPD (p = 0.023) were associated with OSA severity. Positive screening findings (nodules ≥6 mm) were associated with nocturnal hypoxemia on multivariate analysis adjusted for confounders (OR = 2.6, 95% CI = 1.12-6.09, p = 0.027). CONCLUSION: Moderate to severe OSA is very prevalent in patients enrolled in a lung cancer screening program. Nocturnal hypoxemia more than doubles the risk of positive screening findings.

Improving the cadmium-induced centriacinar emphysema model in rats by concomitant anti-oxidant treatment.

1. The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N-acetylcysteine (NAC) administration. 2. Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2- and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3. Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4. Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2-treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 +/- 2 vs 127 +/- 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2-treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2-treated rats. 5. In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2-induced fibrotic component of centriacinar emphysema.

Pulmonary ceroidosis.

We describe a patient with pulmonary ceroid histiocytosis. Skin pigmentation, chest x-ray film and laboratory findings were normal. Only pulmonary function tests were abnormal (TLC = 63 percent, DLco = 52 percent). Based on these functional data, the patient was submitted to a lung biopsy by thoracotomy. Brown pigmented histiocytes were shown occupying alveolar spaces. Similar brown pigmented hepatocytes were seen in the liver biopsy.

Lower pulmonary diffusing capacity in the prone vs. supine posture.

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Qc). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, Dl(CO) was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: Dl(CO,corr) supine vs. prone: 32.6 +/- 2.3 (SE) vs. 30.0 +/- 2 ml x min(-1) x mmHg(-1) stpd; RB: Dl(CO,corr) supine vs. prone: 30.2 +/- 2.2 (SE) vs. 27.8 +/- 2.0 ml x min(-1) x mmHg(-1) stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Qc between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.

Multiple-breath washout experiments in rat lungs.

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.

Single-breath washout experiments in rat lungs.

Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2-5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath-hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (approximately 15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were greater than 1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree.

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.

[Non-invasive ventilation in patients with severe hypercapnic encephalopathy in a conventional hospital ward]. / Ventilación no invasiva en pacientes con encefalopatía hipercápnica grave en una sala de hospitalización convencional.

OBJECTIVE: To report our experience with non-invasive ventilation (NIV) at two levels of pressure (Bi-PAP) on a general respiratory medicine ward with patients in hypercapnic impaired consciousness and/or coma who had not previously been in an intensive care unit (ICU). METHODS: This was a prospective study of 13 patients, mean age 81 years (65-96), treated with NIV through a face mask. Ten had chronic obstructive pulmonary disease, with a mean FEV1 in stable condition of 35.2 14.6%. Glasgow scores upon admission were >/= 7. Arterial gases were monitored until suspension of NIV. RESULTS: After NIV for a mean 19 5 h/day in the first 48 hours and later of 6 1 h/day until a total of 74 9 h, 9 patients (69%) survived. The mean initial pH for these patients was 7.17 0.028 and the mean initial pCO2 was 101 9 mm Hg. In 7 cases (78%), coma was reversed in the first 48 h and a significant improvement in pH was observed in the 12-24 h analysis. Mean pH upon discharge was 7.44 0.013 and mean pCO2 was 54 2.8 mmHg. Four patients died, even though their initial or subsequent arterial gases at 12-24 h were not significantly different from those of the survivors. CONCLUSION: NIV on a general respiratory medicine ward can offer an alternative to oro-tracheal intubation for patients with hypercapnic impaired consciousness and/or coma who do not meet the criteria for admission to the ICU.

[Reliability of Venturi oxygen therapy systems]. / Fiabilidad de los sistemas de Venturi en la oxigenoterapia.

Venturi systems are among the most widely used devices for delivering oxygen therapy. Nevertheless, rigorous quality control of their reliability is lacking. In this study we used mass spectrometry to evaluate Venturi systems sold by various companies in Spain. We also studied tolerance under various conditions (changes in oxygen flow and with increased system resistance). Fixed systems were found to comply well with recommendations, whereas none of the variable systems complied. One system (Oxigem Variable) was unable to provide an oxygen concentration below 31% when set to deliver at 24% to 28%. We conclude that the variable masks available in Spain do not comply with European Union recommendations and the range of error of one of them (Oxigem Variable) means it is not clinically useful. Fixed systems were the most reliable ones in our market, and airlife and intersurgical devices were the variable systems that best approximated the reliability of fixed systems.

Increased collagen deposition correlated with lung destruction in human emphysema.

BACKGROUND: To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. METHODS: Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. RESULTS: The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. CONCLUSIONS: Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema.

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung (i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium-3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134 +/- 25 microm) versus control (85 +/- 14 microm). The apparent diffusion coefficients were significantly different between the two groups (0.18 +/- 0.02 and 0.15 +/- 0.01 cm2 x s(-1) for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.

Effects of inspiratory and expiratory time and high mouth pressures on calculated DLCO by the single-breath procedure. Results with different methods to measure the effective breath-holding time.

We have studied the influence of several manoeuvres modifying inspiratory and expiratory flow, with and without an external obstruction, on measured single-breath diffusing capacity (DLCO). By this method, we could evaluate the effects of increased inspiration or expiration time, independently of the influence of high (negative or positive) mouth pressures. Ten tests were performed in each of 11 trained normal subjects. The sequence of repeated manoeuvres was as follows: (1) basal; (2) inspiratory obstruction (IO); (3) expiratory obstruction (EO); (4) slow inspiration without obstruction (SI), and (5), slow expiration without obstruction (SE). A second, inverted sequence was then performed. The obstructive manoeuvres were forced by a unidirectional valve with a circular hole of 5 mm in diameter. Mouth pressures were registered. The slow flows were voluntarily controlled to be similar to the corresponding flows during the obstructive manoeuvre (approximately 15% of each vital capacity/second). Determinations of breath-holding time (tBH) were calculated by the methods of Jones-Meade, Ogilvie and the American Epidemiology Standardization Project (ESP), but using the same expiratory sample. We found that (DLCO) obtained with the three methods were statistically different (p less than 0.0001) from each other for all manoeuvres. Regarding the basal manoeuvre, there were statistical differences (p less than 0.01) with SI on the Jones-Meade, with IO on the ESP and with SI and IO on the Ogilvie timing methods. Between IO and SI, statistical differences (p less than 0.01) were observed in the three methods, but there was no statistical difference between SE and EO by any method.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome.

The aim of this trial was to evaluate the effectiveness of continuous positive airway pressure (CPAP) in patients with mild sleep apnea- hypopnea syndrome (SAHS). One hundred forty-two consecutive patients with mild SAHS (apnea-hypopnea index 10-30, without severe sleepiness) were randomly assigned to receive conservative treatment (CT)-sleep hygiene and weight loss-(65 patients) or CT plus CPAP (77 patients), and 125 patients (86% males, age: 54 +/- 9 yr, BMI: 29 +/- 4 kg/m(2), AHI: 20 +/- 6, ESS: 12 +/- 4) completed the follow-up. The following outcomes were assessed at inclusion and after 3 and 6 mo of treatment: sleepiness (Epworth scale, multiple sleep latency test [MSLT]), other symptoms related to SAHS, cognitive function, and perceived health status (Functional Outcomes of Sleep Questionnaire [FOSQ], Nottingham Health profile). The relief of SAHS-related clinical symptoms was significantly greater in the CPAP group than in the CT group; the Epworth scale and FOSQ also showed more improvement in the CPAP group but did not reach significance. There were no significant differences in the other tests performed probably because the baseline values were normal. CPAP compliance was 4.8 +/- 2.2 h and treatment continuation was accepted by 62% of the patients at the end of the study. These results suggest that CPAP can be considered in treating patients with mild SAHS on the basis of an improvement in symptoms.

Effect on single-breath washout and lung function of elastase-induced emphysema in rats.

Lung volumes, diffusing capacity (DLCO), quasi-static pressure-volume curves (P-V), forced expiration (FE) and He-SF6 single-breath washout (SBW) were performed in Wistar rats with emphysema induced by different doses of pancreatic elastase in saline, instilled intratracheally 6 wk prior to the tests. Emphysema was quantitatively assessed by mean linear intercept (Lm) measurements on 5-microns lung sections. Lung volume, P-V curve, and FE dependence on Lm, as well as the nonsignificant dependence of DLCO on Lm, are generally similar to results reported by others. The most interesting observation concerns the SBW: N2 slopes of the alveolar plateau, compared for identical lung volumes, did not change with the degree of emphysema. By contrast, the He-SF6 slope difference did depend significantly on the degree of emphysema. Based on the diffusion front theory, the present work suggests that in rats with elastase-induced emphysema, the phase III slope modifications relate mainly to elastic and not to structural alterations.

Pulmonary parenchymal tissue volume and pulmonary capillary blood flow in normal subjects.

We measured pulmonary parenchymal tissue volume (Vt) and pulmonary capillary blood flow (Qc) in 11 normal subjects by a rebreathing technique and end-tidal, dead-space correction (ETDS) method, using two soluble gases, acetylene (C2H2) and dimethyl ether (DME). We assessed the results using different intervals of measurement, inspired volumes and rebreathing frequencies. The mean values +/- SD of Vt were 559 +/- 58 and 511 +/- 52 ml, with C2H2 and DME, and of Qc were 3.67 +/- 0.44 and 4.18 +/- 0.54 liter/min/m2, respectively. Measurements with the interval between the 1st and the 6th end-tidal points and within the first 15 s yielded the best reproducibility. Data obtained from two satisfactory recordings from the same subject are sufficient to calculate Vt and Qc. Inspired volume shows a significant correlation with Vt values measured with both tracer gases, especially with DME. Rebreathing frequency also affects this latter gas. Despite some problems which are not easily explainable (dependence upon the inspired volume, rebreathing frequency and test gas species), we conclude that the methods allow measurements of Vt and Qc with acceptable reproducibility but that different variables may affect the results.