The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CFTR loss of function and of an abnormal interaction between CFTR and ENaC. A few patients were described with CF-like symptoms, a single CFTR mutation and an ENaC mutation.

To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by dHPLC followed by direct sequencing, whereas the SCNN1A, SCNN1B and SCNN1G subunits of ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation

Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these 5 patients detected 8 ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S, c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group.

Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.

Epidemiologic studies indicate that chronic cough and sputum production are associated with increased mortality and disease progression in COPD subjects. Our objective was to identify features associated with chronic cough and sputum production in COPD subjects.

Cross-sectional analysis of data were obtained in a multicenter (17 university hospitals in France) cohort of COPD patients. The cohort comprised 433 COPD subjects (65 ± 11 years; FEV₁, 50 ± 20% predicted). Subjects with (n = 321) and without (n = 112) chronic cough and sputum production were compared.

No significant difference was observed between groups for age, FEV₁, body mass index, and comorbidities. Subjects with chronic cough and sputum production had increased total mean numbers of exacerbations per patient per year (2.20 ± 2.20 vs 0.97 ± 1.19, respectively; p < 0.0001), moderate exacerbations (1.80 ± 2.07 vs 0.66 ± 0.85, respectively; p < 0.0001), and severe exacerbations requiring hospitalizations (0.43 ± 0.95 vs 0.22 ± 0.56, respectively; p < 0.02). the total number of exacerbations per patient per year was the only variable independently associated with chronic cough and sputum production. Frequent exacerbations (two or more per patients per year) occurred in 55% vs 22% of subjects, respectively, with and without chronic cough and sputum production (p < 0.0001). Chronic cough and sputum production and decreased FEV₁ were independently associated with an increased risk of frequent exacerbations and frequent hospitalizations.

Chronic cough and sputum production are associated with frequent COPD exacerbations, including severe exacerbations requiring hospitalizations.

Continuous positive airway pressure (CPAP) is a noninvasive respiratory support technique that may prevent pulmonary complications following cardiac surgery. This study was conducted in order to determine the efficacy of prophylactic nasal CPAP (nCPAP) compared to standard treatment. The primary endpoints were pulmonary adverse effects defined as hypoxemia (PaO₂/F_iO₂<100), pneumonia, and reintubation. The secondary endpoint was the readmission rate to ICUs (ICU) or intermediate care unit (IMCU).

We prospectively randomized 500 patients scheduled for elective cardiac surgery. Following extubation either in the operating theater (early) or in the ICUs (late) patients were allocated to standard treatment (control) including 10 min of intermittent nCPAP at 10cmH₂O every 4h or prophylactic nasal CPAP (study) at an airway pressure of 10cmH₂O for at least 6h.

Prophylactic nCPAP significantly improved arterial oxygenation (PaO₂/FIO₂) without altering heart rate and mean arterial BP. Pulmonary complications including hypoxemia (defined as PaO₂/FIO₂<100), pneumonia, and reintubation rate were reduced in study patients compared to controls (12 of 232 pts. vs 25 of 236 pts., p = 0.03). The readmission rate to ICU or IMCU was significantly lower in nCPAP-treated patients (7 of 232 pts. vs 14 of 236 pts, p = 0.03).

The long-term administration of prophylactic nCPAP following cardiac surgery improved arterial oxygenation, reduced the incidence of pulmonary complications including pneumonia and reintubation rate, and reduced readmission rate to ICU or IMCU. Thus, noninvasive respiratory support with nCPAP is a useful tool to reduce pulmonary morbidity following elective cardiac surgery.

We studied the reasons why thoracenteses performed in our outpatient pulmonary clinic had a higher frequency of iatrogenic pneumothorax compared to our institution's concurrent radiology practice, which utilizes ultrasound guidance. We reviewed our practice model and implemented a unique experiential training paradigm in a zero-risk simulation environment to improve efficacy, timeliness, service orientation and safety.

We retrospectively determined the rate of clinically significant pneumothoraces in our practice (Phase I: July 1, 2001 – June 30, 2002). Training system re-design included: 1) a designated group of pulmonologist instructors dedicated to pleural disease and reduction of iatrogenic complications. 2) use of ultrasound image guidance for all thoracenteses, and 3) structured proficiency and competency standards for proceduralists. Post-intervention, (Phase II), data were prospectively collected (Jan 2005 – Dec 2006) and compared with our baseline data.

The baseline rate of pneumothorax was 8.6% (5 of 58) in our pulmonary practice. Following intervention (Phase II), the rate of pneumothorax declined to 1.1% (p = 0.0034). During Phase II, the number of thoracenteses performed increased (186 per year vs 58, p < 0.05). Iatrogenic pneumothorax rate was stable in the two years following intervention (0.7% [1 of 137] in 2005 and 1.3% [3 of 226] in 2006; p > 0.9). Post-intervention complications included procedure-related pain (N = 19), cough (N = 4), and hypotension (N = 10).

An improvement program that included simulation, ultrasound-guidance, competency testing, and performance feedback reduced iatrogenic risk to patients. We recommend application of this process to procedural practices.

Elderly patients with idiopathic pulmonary embolism (PE) are at high risk for recurrent venous thromboembolic disease and might benefit from long-term anticoagulant therapy. However they are also at higher risk for bleeding complications. Because there are no clinical trials addressing PE treatment in elderly patients, the balance of therapeutic benefits and risks is unclear.

We constructed a decision-analytic model to forecast the effects of long-term warfarin therapy for idiopathic PE. We focused on 65 and 80 year-old outpatients, with or without a propensity for falls, who previously completed 6–12 months of anticoagulant therapy without suffering a major bleed. The model incorporated age-appropriate thromboembolic recurrence rates after PE, major bleeding risks of warfarin use, and the contribution of falls to major bleeding episodes in anticoagulated elderly patients. We used probabilistic sensitivity analysis to model outcomes over ranges of potential thromboembolic and bleeding risks.

In our baseline analysis, long-term warfarin was superior to conventional duration therapy. Depending on the patient subgroup (stratified by age and fall risk), it increased life expectancy by 0.16–0.56 years, and event-free life expectancy by 0.32–0.51 years. Probabilistic sensitivity analysis demonstrated that long-term warfarin was likely to increase life expectancy when compared to conventional-duration therapy (76–93% likelihood across all groups).

Extending anticoagulation for idiopathic PE may be beneficial in a subgroup of elderly patients who tolerate the initial 6–12 months without bleeding complications. In this population, advanced age and fall risk were not contraindications to long-term anticoagulation.

Poor compliance and initial intolerance limit the effectiveness of continuous positive airway pressure (CPAP) in obstructive sleep apnea. Short-term compliance has been shown to predict long-term use. Unfortunately, few identified variables reliably predict initial CPAP tolerance and use. We sought to identify potential pretreatment variables that would predict short-term use of CPAP.

We performed a retrospective review assessing short-term CPAP compliance after 4 to 6 weeks of treatment. Consecutive patients initiating CPAP therapy were included. Demographic and polysomnographic variables were correlated with objective measures of CPAP use. The average hours per night and percentage of nights of CPAP use were correlated with each variable. Variables were also associated with good vs poor compliance, which we defined as ≥ 4 h per night ≥ 70% of nights.

We included 400 consecutive patients (78% male; mean age, 47 ± 8 years). Of the measured variables, only age (48 ± 8 years vs 46 ± 7 years, p = 0.02) and use of a sedative/hypnotic during CPAP titration (77% vs 57.6%, p < 0.0005) were associated with better compliance. Those receiving a sedative/hypnotic had longer sleep times (345 ± 42 min vs 314 ± 51 min, p < 0.0005) and greater sleep efficiency (84 ± 9% vs 78 ± 11%, p < 0.0005) during polysomnography. CPAP titrations were improved in those receiving sedative/hypnotics, achieving lower respiratory disturbance index on the final CPAP pressure (6 ± 7 vs 10 ± 11, p = 0.04).

Of the measured variables, only age and a one-time use of sedative/hypnotics during polysomnography correlated with greater short-term CPAP compliance. Hypnotics facilitated better quality CPAP titrations. Reliable predictors of short-term CPAP use could help identify measures to improve long-term compliance.

In May 2005, the lung allocation score (LAS) was introduced as a means of allocating donor lungs in order to decrease waitlist mortality and prioritize candidates based on medical urgency and post-transplant survival. The purpose of this study was to assess changes in recipient waitlist times and mean LAS since the introduction of the LAS model.

UNOS provided de-identified patient-level data. The study population consisted of all patients in the United States with a reported LAS (n = 3529) undergoing lung transplantation between 5/7/05 and 11/7/07. The study period was divided into six-month intervals. The Kruskal-Wallis test was used to assess differences in variables with nonparametric distributions. The nonparametric trends test was used to determine significance of trends over time.

There was a significant decrease in waitlist time during the study period while LAS among transplant recipients increased (p < 0.001). There was no significant change in FVC (49.3 ± 17.5%, p = 0.48) or PCWP (11.1 ± 5.8 mm Hg, p = 0.23), however, there was a significant increase in age (51.5 ± 13.9 years, p < 0.001) during the study period. When stratified by etiology, the LAS increased for both IPF and COPD patients (p < 0.001). Moreover, the overall number of patients listed for transplantation as well as the LAS among transplant candidates increased (p < 0.001).

Two years after initiation of the LAS model, waitlist times continue to decrease while mean LAS continues to increase. This increase in LAS among transplant recipients is observed most notably in patients with IPF and COPD, and reflected in an increase mean LAS at the time of listing.

Mycobacterium tuberculosis (MTB)-specific interferon- release assays (IGRAs) are an alternative or adjunct to the tuberculin skin test (TST) in identifying recent contacts with latent tuberculosis infection (LTBI), but there are scarce data directly comparing performance of the tests.

To evaluate the agreement between both IGRAs and to determine which contacts were most likely to represent LTBI, the QuantiFERON-TB-Gold In Tube assay (QFT) and the T-Spot.TB test (T-Spot) were compared in TST-positive persons recently exposed to pulmonary tuberculosis cases.

Prospectively enrolled close contacts (n = 812) of 123 culture-confirmed tuberculosis source cases underwent IGRA testing using standardized collected data. Factors independently influencing the risk of MTB infection and their interactions with each other were evaluated by multivariate analysis.

Five variables were found to significantly predict a positive IGRA test result (age, source case acid-fast bacilli positive and/or coughing, cumulative exposure time, foreign origin). There was excellent agreement between the two IGRAs (93.9%, = 0.85), with QFT finding 30.2% of contacts positive and T-Spot finding 28.7%. Assuming positivity to both IGRAs as true infection, sensitivity of the TST at ≥ 10 mm was 72% and at ≥ 15 mm was 39.7%. The use of either IGRA as a replacement for the TST would decrease the number of LTBI suspects to be investigated by approximately 70%.

IGRAs are a more accurate indicator of the presence of LTBI than the TST. Both QFT and T-Spot appear to be valuable public health tools, showing excellent agreement with each other.

Hypoxemia, hypercarbia, and pulmonary arterial hypertension are known complications of advanced COPD. We sought to identify genetic polymorphisms associated with these traits in a population with severe COPD from the National Emphysema Treatment Trial (NETT).

In 389 participants from the NETT Genetics Ancillary Study, single nucleotide polymorphisms (SNPs) were genotyped in five candidate genes previously associated with COPD susceptibility (EPHX1, SERPINE2, SFTPB, TGFB1, and GSTP1). Linear regression models were used to test for association between these SNPs and three quantitative COPD-related traits – PACO₂, PACO₂, and peak pulmonary artery pressure. Genes associated with hypoxemia were tested for replication in probands from the Boston Early-Onset COPD Study.

In the NETT Genetics Ancillary Study population, SNPs in EPHX1 (p = 0.01–0.04) and SERPINE2 (p = 0.04–0.008) were associated with hypoxemia. One SNP within SFTPB was associated with pulmonary artery pressure (p = 0.01). In probands from the Boston Early-Onset COPD Study, SNPs in EPHX1 and in SERPINE2 were associated with the requirement for supplemental oxygen.

In participants with severe COPD, SNPs in EPHX1 and SERPINE2 are associated with hypoxemia in two separate study populations, and SNPs from SFTPB are associated with pulmonary artery pressure in the NETT participants.

In the United States, cases of human blastomycosis are largely described in defined geographic areas, with Mississippi reporting the highest prevalence of disease in the southeast region. The infection is uncommonly recognized in mountainous areas, and our previous report of blastomycosis in the southern Appalachian mountains of northeast Tennessee appeared to be an exception to the usual disease distribution.

Our current retrospective study was undertaken to determine whether blastomycosis has persisted as an endemic fungal infection in our northeast Tennessee geographic area and whether epidemiologic features have changed over a 25-year time period.

Results show that clinical aspects of the disease have remained fairly constant with few exceptions; mass-type pulmonary lesions have become more common, and itraconazole has emerged as the therapy of choice. Most notably, however, are the observations that blastomycosis persists as a major endemic fungal infection in our mountain region, more than half of all cases occurring during the period from 1996 to 2005 were found in a core area centered on two counties, Washington and Unicoi; three of five counties surrounding the core counties experienced rate increases compared to our previous study.

These findings suggest a further expansion of this endemic fungal disease beyond the core region.

Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patient's respiratory drive as reflected by the diaphragm electrical activity (EAdi). We examined to what extent NAVA can unload inspiratory muscles, and whether unloading is sustainable when implementing a NAVA level identified as adequate (NAVAAL) during a titration procedure.

Fifteen adult, critically ill patients with a PaO₂/fraction of inspired oxygen (FIO₂) ratio < 300 mm Hg were studied. NAVAAL was identified based on the change from a steep increase to a less steep increase in airway pressure (Paw) and tidal volume (VT) in response to systematically increasing the NAVA level from low (NAVAlow) to high (NAVAhigh). NAVAAL was implemented for 3 h.

At NAVAAL, the median esophageal pressure time product (PTPes) and EAdi values were reduced by 47% of NAVAlow (quartiles, 16 to 69% of NAVAlow) and 18% of NAVAlow (quartiles, 15 to 26% of NAVAlow), respectively. At NAVAhigh, PTPes and EAdi values were reduced by 74% of NAVAlow (quartiles, 56 to 86% of NAVAlow) and 36% of NAVAlow (quartiles, 21 to 51% of NAVAlow; p < 0.005 for all). Parameters during 3 h on NAVAAL were not different from parameters during titration at NAVAAL, as follows: VT, 5.9 mL/kg predicted body weight (PBW) *[quartiles, 5.4 to 7.2 mL/kg PBW]; respiratory rate (RR), 29 breaths/min (quartiles, 22 to 33 breaths/min); mean Paw, 16 cm H₂O (quartiles, 13 to 20 cm H₂O); PTPes, 45% of NAVAlow (quartiles, 28 to 57% of NAVAlow); and Eadi, 76% of NAVAlow (quartiles, 63 to 89% of NAVAlow). PaO₂/FIO₂ ratio, PACO₂, and cardiac performance during NAVAAL were unchanged, while Paw and VT were lower, and RR was higher when compared to conventional ventilation before implementing NAVAAL.

Systematically increasing the NAVA level reduces respiratory drive, unloads respiratory muscles, and offers a method to determine an assist level that results in sustained unloading, low VT, and stable cardiopulmonary function when implemented for 3 h.

Pharmacotherapy for restless legs syndrome may be ineffective or complicated by side effects. Uncontrolled series using pneumatic compression devices have been shown to reduce symptoms of restless legs syndrome. We sought to assess the efficacy of pneumatic compression devices as a nonpharmacologic treatment for restless legs syndrome.

Prospective, randomized, double-blinded, sham-controlled trial of individuals with restless legs syndrome. Subjects wore therapeutic or sham device prior to the usual onset of symptoms for a minimum of one hour daily. Measures of severity of illness, quality of life, daytime sleepiness and fatigue were compared at baseline and after one month of therapy.

Thirty-five subjects were enrolled. Groups were similar at baseline. Therapeutic pneumatic compression devices significantly improved all measured variables compared to shams. Restless Legs Severity Score improved from 14.1 ± 3.9 to 8.4 ± 3.4 (p = 0.006) and Johns Hopkins Restless Legs Scale improved from 2.2 ± 0.5 to 1.2 ± 0.7 (p = 0.01). All quality of life domains improved more with therapeutic than sham devices (social function 14% vs 1%, p = 0.03; daytime function 21% vs 6%, p = 0.02; sleep quality 16% vs 8%, p = 0.05; emotional well-being 17% vs 10%, p = 0.15). Both Epworth Sleepiness Scale (6.5 ± 4.0 vs 11.3 ± 3.9, p = 0.04) and fatigue (4.1 ± 2.1 vs 6.9 ± 2.0, p = 0.01) were improved compared to sham devices. Complete relief occurred in one-third of subjects using therapeutic and in no subjects using sham devices.

Pneumatic compression devices resulted in clinically significant improvements in symptoms of restless legs syndrome compared to sham devices and may be an effective adjunctive or alternative therapy for restless legs syndrome.

The Agency for Healthcare Research and Quality ranks prevention of venous thromboembolism (VTE) as a top priority for patient safety, however, no guidelines or population-based research exist to guide management for podiatric surgery patients. The objective of our study was to determine the incidence and risk factors for post-procedure VTE in podiatric surgery.

A five-year retrospective analysis of patients undergoing podiatric surgery in a large not-for-profit health maintenance organization serving > 485,000 members in the Pacific Northwest from 1999 to 2004.

We identified 16,804 surgical procedures in 7,264 patients and detected 22 symptomatic post-procedure VTEs. The overall incidence of post-procedure VTE was 0.30%. Three risk factors were significantly and independently associated with VTE in podiatric surgery: prior VTE (incidence 4.6%, RR 23.0, p < 0.001), use of hormone replacement therapy or oral contraceptives (incidence 0.55%, RR 4.2, p = 0.01) and obesity (incidence 0.48%, RR 3.0, p = 0.02).

We identified a low overall risk of VTE in podiatric surgery suggesting that routine prophylaxis is not warranted. However, for patients with a history of prior VTE, peri-procedure prophylaxis is suggested based on the level of risk. For podiatry surgery patients with two or more risk factors for VTE, peri-procedure prophylaxis should be considered. Until a prospective study is completed testing recommendations, guidelines and care decisions for podiatric surgery patients will continue to be based on retrospective data, expert consensus, and clinical judgment.

Air pollution triggers asthma attacks hours to days after exposure. It remains unclear whether socioeconomic deprivation modulates these effects. Investigation of these interactions requires adequate statistical power, obtainable by using either a sufficient number of observations or very sensitive indicators of asthma attacks. Using a small-area temporal ecological approach, we studied the short-term relations between ambient air pollution and sales of short-acting β agonist (SABA) drugs, a frequent and specific treatment for control of asthma attacks in children and young adults and then tested the influence of deprivation on these relations.

The study took place in Strasbourg (France), in 2004. Health insurance funds provided data on 15,121 SABA sales for patients aged 0–39 years. Deprivation was estimated by small geographic areas, by an index constructed from census data. Daily average ambient concentrations of particulate matter (PM₁₀), nitrogen dioxide (NO₂) and ozone (O₃) were modeled on a small-area level. Adjusted case-crossover models were used for statistical analysis.

10-µg.m^-3 increases in ambient PM₁₀, NO₂ and O₃ concentrations were associated respectively with increases of 7·5 (95% CI: 4; 11·2), 8·4 (95% CI: 5; 11·9) and 1 (95% CI: –0·3; 2·2) percent in SABA sales. Deprivation had no influence on these relations.

The associations observed are consistent with those reported by studies focusing on SABA use. Similar studies in other settings should confirm whether the lack of interaction with deprivation is due to specific local conditions.

Although diaphragmatic motion is readily studied by ultrasonography, the procedure remains poorly codified. The aim of this prospective study was to determine the reference values for diaphragmatic motion as recorded by M-mode ultrasonography.

210 healthy adult subjects (150 men, 60 women) were investigated. Both sides of the posterior diaphragm were identified and M-mode was used to display the movement of the anatomical structures. Examinations were performed during quiet breathing, voluntary sniffing and deep breathing. Diaphragmatic excursions were measured from the M-mode sonographic images. In addition, the reproducibility (inter and intra-observer) was assessed.

Right and left diaphragmatic motions were successfully assessed during quiet breathing in all subjects. During voluntary sniffing, the measurement was always possible on the right side and in 208 of 210 volunteers on the left side. During deep breathing an obscuration of the diaphragm by the descending lung was noted in subjects with marked diaphragmatic excursion. Consequently, right diaphragmatic excursion could be measured in 195 out of 210 subjects and left diaphragmatic excursion in only 45 subjects. Finally, normal values of both diaphragmatic excursions were determined. Since the excursions were larger in men than women; the gender needs to be taken into account. The lower limit values were close to 0.9 for women and 1cm for men during quiet breathing, 1.6 for women and 1.8cm for men during voluntary sniffing and 3.7 for women and 4.7cm for men during deep breathing.

We demonstrated that M-mode ultrasonography was a reproducible method for assessing hemidiaphragmatic movement.

Helium-hyperoxia reduces dyspnea and increases exercise tolerance in patients with COPD. We investigated whether breathing helium-hyperoxia would allow patients to perform a greater intensity of exercise and improve the benefits of a pulmonary rehabilitation program.

Thirty-eight nonhypoxemic patients with COPD (FEV₁=47 ± 17%_pred) were randomized to rehabilitation breathing helium-hyperoxia (60:40 He:O₂; n = 19) or air (n = 19). Patients cycled for 30-min, three days/week for six weeks breathing the assigned gas. Exercise intensity was prescribed from baseline, gas-specific, incremental exercise tests and was advanced as tolerated. The primary outcome was exercise tolerance assessed as a change in constant-load exercise time (CLT) following rehabilitation. Secondary outcomes were changes in exertional symptoms, health related quality of life (HRQOL: Short-form 36 and St George’s respiratory questionnaire [SGRQ]) and peak oxygen consumption (VO_2peak) during an incremental exercise test.

The helium-hyperoxia group had a greater change in CLT following rehabilitation compared to air (9.5 ± 9.1 vs 4.3 ± 6.3 min, p < 0.05). At an exercise isotime, dyspnea was significantly reduced in both groups, while leg discomfort only decreased in the helium-hyperoxia group. The changes in exertional symptoms and VO_2peak were not different between groups. HRQOL significantly improved in both groups, however, the change in SGRQ total score was greater with helium-hyperoxia (–7.6 ± 6.4 vs –3.6 ± 5.6, p < 0.05). During rehabilitation, the helium-hyperoxia group achieved a higher exercise intensity and training duration throughout the program (p < 0.05).

Breathing helium-hyperoxia during pulmonary rehabilitation increases the intensity and duration of exercise training that can be performed and results in greater improvements in CLT for patients with COPD.

In daily clinical work, we often face delayed or recurrent pneumothorax after radiofrequency (RF) ablation for lung tumors, but a large study on this theme has not been done. Thus, we examined the rate of delayed or recurrent pneumothorax after RF ablation for lung tumors and the risk factors associated with its occurrence.

This retrospective study was based on 194 consecutive sessions of percutaneous RF ablation of 220 lung tumors in 68 patients under CT fluoroscopic guidance performed in a single institution. Numerous variables were analyzed to assess risk factors for delayed or recurrent pneumothorax.

Pneumothorax after RF ablation occurred in 82 of 194 ablation sessions (42.3%). Thirty-three of those 82 cases had either delayed (n = 20) or recurrent pneumothorax (n = 13). The other 49 cases had nonprogressive pneumothorax. Only contact of the ground-glass opacity (GGO) that emerged around the ablated lesion with the pleura significantly correlated with the frequency of delayed or recurrent pneumothorax in comparisons between no pneumothorax vs delayed/recurrent pneumothorax and between nonprogressive pneumothorax vs delayed/recurrent pneumothorax. Mean period before confirmation of the presence or recurrence of pneumothorax was 24.0 ± 66.4 h. Among the 33 cases with delayed or recurrent pneumothorax, 4 patients needed additional treatment.

Our results indicated that delayed or recurrent pneumothorax is relatively frequently encountered after RF ablation of lung tumors. Particularly, when contact of GGO after RF ablation with the pleura is seen, care must be taken with regard to occurrence of delayed or recurrent pneumothorax.

Traditionally, ventilatory limitation to exercise is assessed by measuring the breathing reserve (BRR), ie, the difference between minute ventilation at peak exercise and maximum voluntary ventilation measured at rest. Recent studies have however, documented important abnormalities in ventilatory adaptation with a remarkable potential to limit exercise even in the presence on a normal BRR. Among them is lung hyperinflation and expiratory flow limitation. This was documented by comparing tidal to maximum flow-volume loops (FVLs) collected throughout the test. In the present study we wondered whether the advantages of using such a technique within the classical cardiopulmonary exercise test (CPET) might be obscured by the maneuvers interfering with the main functional parameters of the test, and eventually with interpretation of the CPET.

We studied 18 healthy subjects, 19 patients affected by COPD and 19 patients with chronic heart failure during maximum exercise test on three different study days in a random order. On one occasion the CPET was conducted with no FVLs (CTRL), whereas on the other occasions FVLs were incorporated every one or two minutes (FVL_1-min, FVL_2-min, respectively).

None of the classical cardio-vascular parameters recorded at ventilatory anaerobic threshold or at peak exercise differed between the study days (ANOVA). Furthermore, the coefficients of variation of the main parameters between FVL_1-min and FVL_2-min days vs. CTRL day were well within natural variability thresholds reported in the Literature.

The FVLs appear to not interfere with the main functional parameters used for interpretation of CPET.

We previously noted that older adults admitted to Surgical Intensive Care Units (SICUs) were at high risk for developing delirium. In the current study, we describe the association between the presence of delirium and complications in older SICU patients and describe the association between delirium occurring in the SICU and older adults’ functional ability and discharge placement.

Secondary analysis of prospective, observational, cohort study. Subjects were 114 consecutive patients age 65 and older admitted to a Surgical Critical Care Service. All subjects underwent daily delirium and sedation/agitation screening during hospitalization. Outcomes prospectively recorded included SICU complication development, discharge location, and functional ability (as measured by the KATZ Activities of Daily Living instrument).

Nearly one-third (31.6%) of older adults admitted to a SICU experienced a complication during their ICU stay. There was a strong association between SICU delirium and complication occurrence (p = 0.001). Complication occurrence preceded delirium diagnosis for 16/20 subjects. Subjects who experienced delirium in the SICU were more likely to be discharged to a place other than home (61.3% vs 20.5%, p < 0.0001) and experience greater functional decline (67.7% vs 43.6%, p = 0.023) than nondelirious subjects. After adjusting for covariates including severity of illness and mechanical ventilation use, delirium was found to be strongly and independently associated with greater odds of being discharged to a place other than home (odds ratio, 7.20, 95% confidence interval, 1.93–26.82).

Delirium in older surgical ICU patients is associated with complications and an increased likelihood of discharge to a place other than home.

The translation of basic research advances to the clinical arena has been slow and inefficient. With the goal of improving interactions and collaboration between basic science and clinical investigators, we instituted a Translational Research Training Program in Acute Lung Injury to complement our basic science and clinical research training programs in Pulmonary and Critical Care Medicine.

We developed a translational research training program in which trainees select a primary research discipline for rigorous development of skills in either basic science research or clinical research. This primary foundation is complemented by cross-training in the other discipline through a specifically designed program of study. To measure the impact of the program, we analyzed publication rates, co-authorship to reflect collaboration between research disciplines, and publication of papers with a translational focus by members of our division before and after the institution of the Translational Research Training Program.

We describe our new training program, including modifications to preexisting program and development of new components. We found significant increases in multidisciplinary authorship and translational articles following institution of Translational Research Training Program.

An explicit translational research training program appears to increase collaboration between basic and clinical investigators. Our goal is to share our experiences and provide a template for other Pulmonary and Critical Care programs interested in developing similar curricula. We speculate this training will improve the translation of basic research findings into clinical advances, thus increasing the probability that successful treatments will be developed for patients with lung diseases.

Patients with indications for oral anticoagulation (OAC) undergoing percutaneous coronary artery stenting (PCI-S) represent a high-risk population for major bleeding complications. Chronic kidney disease (CKD) is also associated with poor outcome after PCI-S. Limited data are available regarding the impact of CKD on the frequency of major bleeding and mortality in this population.

We investigated the influence of CKD on major bleeding and all-cause mortality in patients with indication for OAC who undergo PCI-S. Patients were grouped according to calculated creatinine clearance (CrCl): CrCl ≥ 60 mL/min, (n = 98) and CrCl < 60 mL/min, (n = 68). Major bleeding and major adverse vascular events (all-cause mortality, myocardial infarction, repeat revascularization, stent thrombosis, or stroke) were collected during follow-up.

We analyzed 166 consecutive patients with indication(s) for OAC (77% men; mean age, 71 years; range, 66 to 76 years) after undergoing PCI-S. CKD was associated with higher risk for major bleeding (hazard ratio [HR], 3.44; 95% confidence interval [CI], 1.50 to 7.93; p = 0.004) and all-cause mortality (HR, 3.50; 95% CI, 1.53 to 7.99; p = 0.003). In multivariate analyses, age ≥ 75 years (HR, 2.75; 95% CI, 1.15 to 6.56; p = 0.023), CKD (HR, 2.59; 95% CI, 1.00 to 6.95; p = 0.049), anemia (HR, 2.36; 95% CI, 1.00 to 5.54; p = 0.049), and triple antithrombotic therapy (HR, 3.29; 95% CI, 1.23 to 8.84; p = 0.018) were independent predictors for major bleeding, whereas age ≥ 75 years (HR, 2.38; 95% CI, 1.03 to 5.59; p = 0.046) and CKD (HR, 2.44; 95% CI, 1.03 to 5.82; p = 0.044) were predictors for all-cause mortality.

In this high-risk population, CKD is independently associated with increased major bleeding and all-cause mortality following PCI-S.

Healthcare-associated pneumonia (HCAP) is a relatively new concept. Epidemiologic studies are limited and initial empirical antibiotic treatment is still under discussion. This study aimed to reveal the differences in mortality and pathogens between HCAP and community-acquired pneumonia (CAP) in each severity class and to clarify the strategy for the treatment of HCAP.

We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized between November 2005 and January 2007, and compared baseline characteristics, severity, pathogen distribution, antibiotic regimens, and outcomes. In each severity class (mild, moderate, and severe) assessed using the A-DROP scoring system, we investigated the in-hospital mortality and occurrence of potential drug-resistant (PDR) pathogens.

A total of 371 patients (141 HCAP, 230 CAP) were evaluated. The proportion of patients in the severe class was higher in HCAP than in CAP patients. In the moderate class, the in-hospital mortality of HCAP patients was significantly higher than that of CAP patients (11.1% vs 1.9%; p = 0.008). In moderate-class patients in whom pathogens were identified, PDR pathogens were isolated more frequently from HCAP than from CAP patients (22.2% vs 1.9%; p = 0.002). The occurrence of PDR pathogens was associated with initial treatment failure and inappropriate initial antibiotic treatment.

The present study provides additional evidence that HCAP should be distinguished from CAP, and suggests that the therapeutic strategy for HCAP in the moderate class holds the key to improving mortality. Physicians may need to consider PDR pathogens in selecting the initial empirical antibiotic treatment of HCAP.

Despite the frequent occurrence of pleural effusions in lung transplant recipients, little is known about early posttransplant pleural space infections. We sought to determine the predictors and clinical significance of pleural infection in this population.

We analyzed 455 consecutive lung transplant recipients and identified patients who had undergone sampling of pleural fluid within 90 days posttransplant. A case-control analysis was performed to determine the characteristics that predict infection and the impact of infection on posttransplant survival.

Pleural effusions undergoing drainage occurred in 27% of recipients (124 of 455 recipients). Ninety-six percent of effusions were exudative. Pleural space infection occurred in 27% of patients (34 of 124 patients) with effusions. The incidence of infection did not differ significantly by native lung disease or type of transplant operation. Fungal pathogens accounted for ≥ 60% of the infections; Candida albicans was the predominant organism found. Bacterial etiologies were present in 25% of cases. Infected pleural effusions had elevated lactate dehydrogenase levels (p = 0.036) and markedly increased neutrophil levels in the pleural space (p < 0.0001) compared to noninfected effusions. A pleural neutrophil percentage of ≥ 21% provides a sensitivity of 70% and a specificity of 79% for correctly identifying an infection. Patients with pleural space infection had a diminished 1-year survival rate compared to those without infection (67% vs 87%, respectively; p = 0.002).

Pleural infection with fungal or bacterial pathogens commonly complicates lung transplantation, and an elevated neutrophil level in the pleural fluid is the most sensitive and specific indicator of infection.

To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP).

Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008.

One hundred forty-five (145) patients were diagnosed with RP. Thirty-one had airway involvement, a prevalence of 21%. Twenty- two were females (70%) and ages were 11–61 years (median 42) at the time of first symptoms.

The clinical characteristics of elderly subjects with ₁ antitrypsin deficiency (AATD)-associated COPD have not been described.

The clinical, demographic, health-related quality of life (HRQoL) characteristics and 1-year exacerbation rates of 275 subjects with AATD and COPD receiving augmentation therapy aged > 59 years (mean 66.3 ± 5.7 years) were compared to those of 354 subjects aged 50–59 years (mean 54.3 ± 2.8 years) and 293 subjects < 50 years (mean 43.9 ± 3.8 years).

Older subjects were diagnosed later in life (mean age 55.0 ± 8.5 years) and had a longer diagnostic delay (12.9 ± 14.3 years) compared to subjects in the other 2 age groups. Although the proportion of lifetime nonsmokers was higher in the older group, still the majority (64%) had significant tobacco exposure but with a longer interval of tobacco abstinence. The mean FEV₁ values (N = 641) were similar between the 3 age groups suggesting a slower disease progression in the oldest group. Subjects in the older group were less symptomatic, had less concomitant asthma and had significantly better scores in most domains of two HRQoL instruments. During follow-up, older subjects had fewer acute exacerbations.

Subjects with AATD-associated COPD that reach an older age exhibit a more indolent clinical course than younger affected individuals, possibly related in part to differences in tobacco exposure. This findings support current guidelines that recommend screening all patients with COPD for AATD regardless of their age and prior smoking history.

Clinical signs often fail to identify stroke patients at increased risk of aspiration. We hypothesized that objective measures of voluntary cough would better predict those at risk.

A comprehensive diagnostic evaluation was completed for 96 consecutive stroke patients that included cognitive testing, a bedside clinical swallow examination, aerodynamic and sound pressure level measures of voluntary cough, and "gold standard" instrumental swallowing studies (videofluoroscopy, VSE or fiberoptic endoscopy, FEES). Stroke severity was assessed retrospectively using the Canadian Neurologic Scale.

Based on VSE/FEES, 33 patients (34%) were at high risk of aspiration and (66%) were nonaspirators. Clinical signs (absent swallow, difficulty handling secretions or reflexive cough after water bolus) had an overall accuracy of 74% with a sensitivity of 58% and a specificity of 83% for the detection of aspiration. Three objective measures of voluntary cough (expulsive phase rise time; volume acceleration, and expulsive phase peak flow) were each associated with aspiration risk category (areas under the curves, AUCs, were 0.93, 0.92 and 0.86, respectively). Expulsive phase rise time ≥ 55 m/s, volume acceleration < 50 L/s/s, and expulsive phase peak flow < 2.9 L/s had sensitivities of 91%, 91%, and 82%, and specificities of 81%, 92% and 83% for the identification of aspirators.

Objective measures of voluntary cough can identify stroke patients at risk for aspiration and may be useful as an adjunct to the standard bedside clinical assessment.

Few studies have addressed the effects of aging on levels of inflammatory markers in exhaled breath condensate (EBC). The aim of this study was to determine whether there are significant age-associated differences in pH, 8-isoprostane, and nitrogen oxide values in EBC from a population of healthy adults.

EBC samples were obtained from 75 healthy volunteers aged 18 to 80 years and stratified into five age groups (n = 15): 18–29, 30–39, 40–49, 50–59 and 60–80. The following were measured in the samples collected: pH before and after deaeration, nitrite, nitrate, and 8-isoprostane. Differences between the groups were assessed by the Kruskal-Wallis test.

Significant differences in deaerated pH (p < 0.0001) were found in the group of individuals 60 to 80 years of age as compared to the remaining groups. Significant differences were also found in 8-isoprostane levels between the younger groups (18–29 and 30–39 years of age) and the oldest group (p = 0.006 and p = 0.034, respectively). There were no significant differences in nitrite or nitrate values between younger and older individuals.

The results of this study indicate that pH and 8-isoprostane levels in EBC show a relationship with age. Thus, values obtained in studies with control groups may require adjustment for these factors.

Methods Induced sputum was obtained from 28 bronchial asthma (BA) subjects, 20 nonasthmatic atopic control (AC) subjects, and 38 nonasthmatic nonatopic normal control (NC) subjects. The microarray samples of subjects were randomly selected from 9 BA, 3 AC and 6 NC subjects. Sputum supernatants were analyzed by RayBio® 0 Custom Human Cytokine Array, designed to analyze 79 specific cytokines simultaneously. The levels of GRO-, eotaxin-2, and pulmonary and activation-regulated chemokine (PARC)/CCL18 were measured by sandwich ELISAs, and eosinophil-derived neurotoxin (EDN) was measured by RIA.

By microarray, the signal intensities for GRO-, Eotaxin-2, and PARC were significantly higher in BA subjects than in AC and NC subjects (p = 0.036, p = 0.042 and p = 0.033, respectively). By ELISA, the sputum PARC protein levels were significantly higher in BA subjects than in AC and NC subjects (p < 0.0001, respectively). Furthermore PARC levels correlated significantly with sputum eosinophil percentages (r = 0.570, p < 0.0001) and the levels of EDN (r = 0.633, p < 0.0001), RANTES (r = 0.440, p < 0.001), IL-4 (r = 0.415, p < 0.01) and IFN-|gg (r = 0.491, p < 0.001).

By a nonbiased screening approach, a chemokine, PARC, is elevated in sputum specimens from patients with asthma. PARC may play important roles in development of airway eosinophilic inflammation in asthma.

Although alveolar epithelial injury is a major determinant of outcome in patients with acute lung injury, there is no reliable biological marker of alveolar epithelial injury. The primary objective was to determine if elevated levels of the receptor for advanced glycation end-products (RAGE) a marker of alveolar epithelial injury, reflect impaired alveolar fluid clearance (AFC) in an ex vivo perfused human lung preparation. A second objective was to determine if levels of a marker of endothelial injury, von Willebrand factor antigen (vWf:Ag), are associated with impaired AFC.

Human lungs (n = 30) declined for transplantation by the California Transplant Donor Network were perfused at a constant pulmonary artery pressure of 12 mm Hg. Following rewarming to 36°SDC, the lungs were inflated with a continuous positive airway pressure of 10 cm H₂O. RAGE and vWf:Ag levels and AFC rates were then measured.

The rate of AFC was inversely correlated with RAGE levels in the alveolar fluid (p < 0.005). Similarly, the concentration of RAGE in the alveolar fluid was significantly higher in lungs with submaximal alveolar fluid clearance, defined in a prespecified analysis as AFC ≤ 14%, when compared with lungs with preserved alveolar fluid clearance (median 0.82 vs 0.43 µg/mL, p < 0.05). In contrast, VWF levels did not correlate with the rate of AFC.

RAGE may be a useful biological marker of alveolar epithelial injury and impaired AFC in donor lungs prior to transplant and perhaps in patients with acute lung injury.

Although depression among COPD patients is a common problem with important consequences for management of COPD and overall outcomes, the proportion that receives guideline concordant depression care is low. Guideline concordant depression care is associated with fewer depressive symptoms and lower risk for psychiatric hospitalization; however, it is unknown whether guideline-concordant depression care favorably impacts COPD-related outcomes for patients with both conditions.

This retrospective cohort study investigated 5517 veterans with COPD that experienced a new treatment episode for depression. Guideline-concordant depression care was defined as having an adequate supply of antidepressant medication and sufficient follow-up care. Multivariate methods were used to examine the relationship between receipt of guideline-concordant depression care and (1) COPD-related hospitalization and (2) all-cause mortality 2 years after the depression episode, while controlling for care setting and other covariates.

There was no association between the receipt of guideline-concordant depression care and COPD-related hospitalization (OR = 0.98) or all-cause mortality (OR = 0.95). However, patients seen in mental health settings during their depressive episode had 30% lower odds of 2-year mortality than patients seen in primary care.

For patients with COPD and depression, interacting with a mental health professional may be an important intervention. However, receiving guideline-concordant depression care as outlined in common quality monitors was not significantly associated with decreased hospitalization or mortality. These findings suggest that more referrals to specialty care or better care coordination with mental health specialty care may lead to a significant reduction in mortality risk for these patients.

Sleepiness in medical residents has crucial implications for the safety of both patients and residents. Measures to improve this have primarily included ACGME mandated reduction in work hours in residency programs. The impact of these work hour limitations has not been consistent. The purpose of this study was to provide an objective assessment of daytime sleepiness in medical residents working in the medical ICUs. Sleep times for 2 days/nights prior to call and on the day/night of on-call were assessed by actigraphy and sleep diaries. On-call and post-call measurements of residents’ sleepiness were measured both objectively, by means of a modified MSLT (2 nap sessions), as well as subjectively, by Stanford Sleepiness Scale.

Our data showed that despite an average sleep time of 7.15 h on nights leading to the call, Mean Sleep Latency (MSL) on the on-call day was 9 +/– 4.4 min compared to the MSL on the post call day of 4.8 +/–4.1 min; p < 0.001. On the post-call day 14 residents (70%) had MSL values < 5 min suggesting severe sleepiness as compared to 6 (30%) on the on-call day.

Our results demonstrate that residents working in the ICU despite reductions in work hours demonstrate severe degree of sleepiness post-call.

Hypoalbuminemia is a reliable predictor of mortality in patients with various illnesses as well as a predictor of disability and mortality in healthy older adults. The association between hypoalbuminemia and mortality in patients with idiopathic interstitial pneumonia remains unknown. The objective of this study was to examine the relationship between serum albumin concentration and mortality in a large cohort of patients with idiopathic interstitial pneumonia listed for lung transplantation.

In patients classified as having idiopathic pulmonary fibrosis, who were listed for lung transplantation with the United Network for Organ Sharing between January 1, 2004, and December 31, 2006 (n = 1,269), we studied the relationship between serum albumin concentration at the time of listing and mortality while awaiting transplantation.

Lower serum albumin was associated with increased mortality rate. Patients with lower categories of serum albumin had increased mortality rates before and after multivariable adjustment (p value for linear trend < 0.0001). Analysis with serum albumin as a continuous predictor indicated that the mortality rate increased by 54% with each 0.5 g/dL decrease in serum albumin concentration (95% confidence interval, 32 to 79%).

Lower serum albumin is strongly and independently associated with higher mortality in patients with idiopathic interstitial pneumonia on transplant-waiting lists.

Variation in hospitalization rates for acute asthma in Ontario may reflect gaps between evidence and current emergency department (ED) management.

To investigate ED management of asthma and differences in practice patterns for pediatric (< 20 years old) and adult (> 20 years old) asthma in Ontario EDs.

Patient characteristics and ED management were assessed by questionnaire and chart abstractions in a stratified sample of 16 Ontario hospitals > 1 year. Variation between sites was assessed by oneway ANOVA, Kruskal-Wallis or |gx² tests.

Reported results are based on the first of 2671 pediatric (42.0% female) and 2078 adult (66.7% female) visits with a corresponding questionnaire. Asthma severity, comorbidities, access to care and prehospital management varied significantly among sites (all p < 0.001). Documentation of peak expiratory flow [27.2% of pediatric (age > 7) and 44.3% of adult charts], and use of systemic steroids in ED (35.2% pediatric and 33.0% adult charts) and on discharge (31.7% pediatric and 33.2% adult charts), and referrals to asthma services (2.8% pediatric and 2.7% adult charts) varied among sites (all p < 0.001). Admission (%) was directly related to time to receive systemic steroids in ED in adults (r = 0.76; p = 0.004). Repeat ED visits (%) were inversely related to new inhaled steroid prescription on discharge in adults (r= –0.64; p = 0.02).

Knowledge translation initiatives are warranted to increase adherence with emergency asthma best practices (such as objective assessment of airflow rates, use of systemic steroids and referrals) in order to reduce variations in care and improve outcomes of severe acute asthma.

Prospective single center study to determine whether the presence of soluble triggering receptor expressed on myeloid cells (sTREM-1) has diagnostic utility in mechanically ventilated patients with pulmonary infiltrates undergoing BAL.

Prospective cohort study.

Barnes-Jewish Hospital, a 1200-bed urban teaching hospital.

Adult patients with acute respiratory failure undergoing BAL for pulmonary infiltrates. Interventions: BAL fluid measurement of sTREM-1 using a Quantikine Human TREM-1 Immunoassay (R&D Systems, Minneapolis, MN, USA).

Measurements and Main Results.A total of 105 consecutive mechanically ventilated patients undergoing BAL were enrolled. Of those, 19 (18.1%) met definite microbiologic criteria for bacterial or fungal ventilator-associated pneumonia (VAP). Though the mean sTREM-1 concentration was greater in patients with definite VAP (n = 19, 171.9 ± 158.7 pg/mL) than in patients with definite absence of VAP (n = 21, 96.7 ± 76.2 pg/mL), this difference was not statistically significant (p = 0.06). A cutoff value for sTREM-1 > 200 pg/mL yielded a diagnostic sensitivity of 42.1% and a specificity of 75.6% for definite VAP. Patients with alveolar hemorrhage had the greatest values for sTREM-1 (n = 9, 555 ± 440 pg/mL). Receiver operating curve analysis and multivariate logistic regression analysis demonstrated that measurement of sTREM-1 was inferior to clinical parameters for the diagnosis of VAP.

Measurement of sTREM-1 in BAL fluid appears to have minimal diagnostic value for VAP.

Right ventricular function is a key determinant of exercise capacity and survival in pulmonary arterial hypertension. We aimed to study the predictors of right ventricular ejection fraction (RVEF) in newly-diagnosed patients with pulmonary arterial hypertension.

We performed a cross-sectional analysis of a retrospective cohort of consecutive patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension who underwent equilibrium radionuclide angiography for measurement of RVEF at baseline.

Of the 84 patients in the cohort, 63 patients underwent equilibrium radionuclide angiography and right heart catheterization and were included. The mean age was 41 ± 13 years and 79% were female. The mean RVEF was 30 ± 8%. RVEF was directly associated with right ventricular stroke volume index and cardiac index and inversely associated with pulmonary vascular resistance index from right heart catheterization (all p ≤ 0.01). Older age and male sex were associated with lower RVEF (p < 0.05) after adjustment for pulmonary vascular resistance index and left ventricular ejection fraction. Higher plasma von Willebrand factor levels were also independently associated with lower RVEF (p < 0.01) (n = 55). Body size and type of pulmonary arterial hypertension were not associated with RVEF.

Older patients and males with PAH had lower RVEF at baseline compared to younger patients and females even after controlling for left ventricular function and hemodynamics. Higher plasma von Willebrand factor levels, a marker of endothelial dysfunction, were also associated with lower RVEF.

Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemo-reflexes resulting in sleep hypoventilation. We report a Chinese family with PHOX2B mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness on its various manifestations.

After identifying central hypoventilation in an adult male (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offsprings. Pulmonary function tests, overnight polysomnography, arterial blood gases, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter, and echocardiography were done on members with clinically diagnosed central hypoventilation.

The index patient and four offsprings manifested with clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit of 70%. The first and fourth children had frequent cyanotic spells and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir SpO₂ of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received BiPAP treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemo-sensitivity.

Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

It is widely believed that children with asthma miss considerably more school than children without asthma. Previous surveys have indicated that 49% of children with asthma miss school (Asthma in America, 1998), but only a few studies have attempted to quantify the amount of school missed. Understanding the role of asthma in school attendance will help direct limited health care resources to the children who need them most.

Funded by the Dallas Asthma Consortium and the Summerfield Roberts Foundation, we investigated school absence rates in fourth-sixth grade students in 19 inner city schools. The sample consisted of 353 students who were identified as possibly asthmatic based on responses to a modified Brief Pediatric Screen instrument and who underwent spirometry and/or exercise testing to confirm the diagnosis of asthma: 25 were excluded for FEV1 \h 70% and without bronchodilator response, while 157 were exercise (+) (EC+), and 171 exercise (-)(EC-). We compared yearly absences for these students with each other, with all 4-sixth graders in the 19 study schools, and with all 4-sixth graders in the district, in addition to tabulating data for school RN identified asthmatics from a separate database. Absence data by school and by grade level was provided by the school district at the end of the from 2002 to 2003 school year.

Absence rates were 2.54% (EC+), 2.12%(EC-), 2.59% (abnormal FEV1), 2.86% (RN identified), 2.85% (all 4-sixth graders in study schools), and 2.95% (all 4-sixth graders in DISD). Conclusion: asthmatic students in the DISD miss no more school than nonasthmatic classmates.

Data examining the role of pulmonary rehabilitation in interstitial lung disease are limited. We tested the hypothesis that pulmonary rehabilitation would improve functional status and dyspnea in a large group of patients with interstitial lung disease, and that certain baseline patient variables could predict this improvement.

Data from patients referred to pulmonary rehabilitation with a diagnosis of interstitial lung disease were included. Baseline and post-pulmonary rehabilitation variables were recorded and changes in 6 min walk distance and dyspnea were evaluated. The impact of baseline variables on change in 6 min walk distance and dyspnea were analyzed.

A statistically significant difference was seen in both the change in Borg score and 6 min walk distance after pulmonary rehabilitation (p < 0.0001). These changes were consistent with previously established clinically significant differences. Baseline 6 min walk distance was a significant predictor of change in 6 min walk distance (p < 0.0001), with increasing baseline 6 min walk distance predicting a smaller improvement after pulmonary rehabilitation.

These results suggest that pulmonary rehabilitation should be considered as standard of care for patients with interstitial lung disease.

During noninvasive ventilation, non intentional leaks have a detrimental effect on the efficacy of ventilation. A wide range of industrial masks are available, with intentional leaks of different importance. The potential impact of this variability in intentional leaks on performances of bi-level ventilators has not been assessed.

To measure intentional leaks in 7 different industrial masks and determine whether higher leaks modify ventilator performances and quality of ventilation.

7 interfaces connected to four ventilators (VPAP3-RESMED^TM; HARMONY2- RESPIRONICS^TM; SMARTAIR-ST-AIROX^TM; GK425ST-TYCO^TM) were adapted on a mannequin connected to a lung model (ASL5000, IngMar Medical^TM). Inspiratory (IPAP) and expiratory pressures were respectively 14 and 4cmH₂O. Lung model was set with a respiratory rate at 15/min and duration of inspiration at 1 s in three simulated conditions (normal, restrictive, obstructive). Inspiratory trigger delay and effort, capacity to achieve and maintain IPAP, expiratory cycling and tidal volume (VT) were analyzed for all masks and ventilators in the three simulated lung conditions.

The level of intentional leaks in the 7 masks ranged from 30 to 45L*min^-1 (for a IPAP of 14cmH₂O). Importance of leaks did not influence trigger performances. However, capacity to achieve and maintain IPAP was significantly decreased with all ventilators and in all simulated lung conditions when intentional leaks increased. This led to a maximum reduction in delivered VT of 48 mL. Expiratory cycling was not affected by the level of intentional leaks except in obstructive lung conditions.

Mask intentional leaks can impair efficacy of ventilation, especially when > 40L*min^-1.

A high prevalence of obstructive sleep apnea (OSA) symptoms was reported in asthma patients. Our goal was to evaluate factors associated with habitual snoring and OSA risk in these patients.

Asthma patients at specialty clinics were surveyed with the Sleep Apnea scale of Sleep Disorders Questionnaire (SA-SDQ) and questions about asthma symptoms frequency (National Asthma Education and Prevention Program guidelines), followed by chart review. SA- SDQ scores ≥ 36 for men and ≥ 32 for women defined high OSA risk. Logistic regression was used to model associations with habitual snoring and high OSA risk.

Among 244 patients, 37% snored habitually and 40% demonstrated high OSA risk. Independent predictors of habitual snoring included gastroesophageal reflux disease (GERD, OR [95%CI]: 2.19 [1.19–4.02]) and use of an inhaled corticosteroid (ICS) (2.66 [1.05–6.72]). High OSA risk was predicted by asthma severity step (1.59 [1.23–2.06]), GERD (2.70 [1.51–4.83]), and ICS use (4.05 [1.56–10.53]). Linear, dose-dependent relationships of ICS with habitual snoring and high OSA risk were seen (p = 0.004 and p = 0.0006, respectively). Women demonstrated a 2.11 times greater odds for high OSA risk [1.10–4.09] when controlling for the above covariates.

Symptoms of OSA in asthmatics are predicted by asthma severity, coexistent GERD, and use of an ICS in a dose-dependent fashion. The well-recognized male gender predominance for OSA symptoms is not apparent in these patients. Further exploration of these relationships may help to explain the increased prevalence of OSA in asthma and provide new insights into the reported female predominance of asthma morbidity.

Arm span is the closest physiologic measurement to standing height. Increased arm span: standing height ratio therefore indicates possible loss of height which is a feature of aging, often resulting from osteoporosis related vertebral collapse. We hypothesize that the discrepancy between arm span and height is associated with reduced airflow volumes, severity of dyspnea, and right-sided cardiac structural changes in older individuals with symptoms of dyspnea.

Patients investigated with transthoracic echocardiography for suspected heart failure were invited to participate in our study. All subjects were evaluated with a clinical history and physical examination followed by measurements of arm span, standing height, weight, forced expiratory volume in one second (FEV1) and FVC.

66 subjects aged 71 ± 10 years were recruited to our study. Arm span: height was significantly negatively correlated with FEV1 (r=–0.464; p < 0.001), FVC (r=–0.479; p < 0.001) and body weight (r=–0.252; p < 0.05), and positively correlated with the New York Heart Association classification for dyspnoea (rho = 0.309; p < 0.05). Female sex, steroid use, inhaled bronchodilators, orthopnoea, paroxysmal nocturnal dyspnoea and right heart chamber dilatation were significantly associated with higher arm span: height.

We have found a significant association between increased arm span: height ratio, reduced respiratory airflow volumes, increased severity of dyspnoea, and echocardiographic features of pulmonary heart disease in a group of predominantly elderly subjects with multiple comorbidities. The role of arm span measurements in assessments of airflow volumes in older patients and the association between loss of height and dyspnea now deserves further evaluation.

Mean pulmonary artery pressure (mPAP) may be estimated by using the classic rule of thumb, namely 2/3dPAP + 1/3sPAP, where dPAP and sPAP are diastolic and systolic pressures. Recent studies have suggested that mPAP may be also estimated from sPAP only. Pulmonary hypertension is usually defined by an invasive mPAP > 25 mm Hg, but the corresponding sPAP threshold remains to be established. Our study evaluated the accuracy and precision of various empirical formulas (F) relating mPAP and sPAP in resting adults.

Five previously published studies with individual high-fidelity PA pressures were analyzed (n = 166 individuals, of whom 57% had pulmonary hypertension). The time-averaged mPAP was compared with F1, the classic rule of thumb; F2 = dPAP + 0.41pPAP, where pPAP is pulse pressure; F3 = sqrt (sPAPxdPAP); F4 = 0.61sPAP + 2mmHg; and F5 = 2/3sPAP (parabolic shape).

The mPAP ranged from 9 to 82 mm Hg and was related to sPAP (r²=0.98). The most accurate formula was F4 (mean bias = 0.0 mm Hg). The most precise formula was F1 (SD of the bias = 1.6 mm Hg). Other formulas gave estimates of essentially similar accuracy, while F2 and F3 were more precise than F4 and F5. A sPAP > 36 mm Hg diagnosed pulmonary hypertension (mPAP > 25 mm Hg) with a 97.9% sensitivity and 98.6% specificity.

In resting adults, the most accurate estimate of mPAP was obtained by using sPAP only, while the combination of sPAP and dPAP gave the most precise mPAP estimate. The 36 mm Hg sPAP threshold value diagnosed pulmonary hypertension with high sensitivity and high specificity.