Differential asthma odds following respiratory infection in children from three minority populations.

RATIONALE: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited. OBJECTIVES: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children. METHODS: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children. MEASUREMENTS AND MAIN RESULTS: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21-9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately. CONCLUSIONS: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans.

Combining qSOFA criteria with initial lactate levels: Improved screening of septic patients for critical illness.

OBJECTIVE: To determine if the addition of lactate to Quick Sequential Organ Failure Assessment (qSOFA) scoring improves emergency department (ED) screening of septic patients for critical illness. METHODS: This was a multicenter retrospective cohort study of consecutive adult patients admitted to the hospital from the ED with infectious disease-related illnesses. We recorded qSOFA criteria and initial lactate levels in the first 6 h of ED stay. Our primary outcome was a composite of hospital death, vasopressor use, and intensive care unit stay ≤72 h of presentation. Diagnostic test characteristics were determined for: 1) lactate levels ≥2 and ≥4; 2) qSOFA scores ≥1, ≥2, and =3; and 3) combinations of these. RESULTS: Of 3743 patients, 2584 had a lactate drawn ≤6 h of ED stay and 18% met the primary outcome. The qSOFA scores were ≥1, ≥2, and =3 in 59.2%, 22.0%, and 5.3% of patients, respectively, and 34.4% had a lactate level ≥2 and 7.9% had a lactate level ≥4. The combination of qSOFA ≥1 OR Lactate ≥2 had the highest sensitivity, 94.0% (95% CI: 91.3-95.9). CONCLUSIONS: The combination of qSOFA ≥1 OR Lactate ≥2 provides substantially improved sensitivity for the screening of critical illness compared to isolated lactate and qSOFA thresholds.

Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico.

BACKGROUND: In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico. METHODS: CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than ​​​​60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools. RESULTS: Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del. CONCLUSIONS: In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.

Severe Sea Lion Bites in Urban Cold-Water Swimmers.

BACKGROUND: A series of sea lion bites in open-water swimmers recently gained the attention of the national and international media. Pinniped (the clade including seals and sea lions) bites historically have been in people who hunt or handle marine mammals. As populations of humans and pinnipeds continue to grow, interactions with animals by those participating in recreational activities are likely to become more frequent. CASE REPORTS: In December of 2017 and January of 2018, four sea lion (Zalophus californianus) bites in humans occurred at a popular open-water recreational swimming area in San Francisco, California. Three swimmers required treatment at a local trauma center and two required surgery. Two of the wounds were potentially life threatening; one swimmer required a field tourniquet to stop bleeding from the antecubital fossa, and the bite in another narrowly missed the femoral artery. The purpose of this report is to offer an in-depth discussion of antimicrobial use and rabies postexposure prophylaxis in patients with severe pinniped bites. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Information from this report can be used in conjunction with input from local experts to develop a thoughtful therapeutic plan for patients with severe pinniped bites. Doxycycline is the first-line antibiotic therapy, but broader coverage may be needed for severe wounds with the potential for contamination. The likelihood of rabies is low, and rabies postexposure prophylaxis should be reserved for cases that involve unusually aggressive animal behavior or other factors suggestive of rabies.

Ambient air pollution, asthma drug response, and telomere length in African American youth.

BACKGROUND: Telomere length (TL) can serve as a potential biomarker for conditions associated with chronic oxidative stress and inflammation, such as asthma. Air pollution can induce oxidative stress. Understanding the relationship between TL, asthma, and air pollution is important for identifying risk factors contributing to unhealthy aging in children. OBJECTIVES: We sought to investigate associations between exposures to ambient air pollutants and TL in African American children and adolescents and to examine whether African ancestry, asthma status, and steroid medication use alter the association. METHODS: Linear regression was used to examine associations between absolute telomere length (aTL) and estimated annual average residential ozone (O3) and fine particulate matter with a diameter of 2.5 µm or less (PM2.5) exposures in a cross-sectional analysis of 1072 children in an existing asthma case-control study. African ancestry, asthma status, and use of steroid medications were examined as effect modifiers. RESULTS: Participants' aTLs were measured by using quantitative PCR. A 1-ppb and 1 µg/m3 increase in annual average exposure to O3 and PM2.5 were associated with a decrease in aTL of 37.1 kilo-base pair (kb; 95% CI, -66.7 to -7.4 kb) and 57.1 kb (95% CI, -118.1 to 3.9 kb), respectively. African ancestry and asthma were not effect modifiers; however, exposure to steroid medications modified the relationships between TL and pollutants. Past-year exposure to O3 and PM2.5 was associated with shorter TLs in patients without steroid use. CONCLUSION: Exposure to air pollution was associated with shorter TLs in nonasthmatic children and adolescents. This was not the case for asthmatic children as a group, but those receiving steroid medication had less shortening than those not using steroids. Reduced exposure to air pollution in childhood might help to preserve TL.

Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.

Trends in the utilisation of emergency departments in California, 2005-2015: a retrospective analysis.

OBJECTIVE: To examine current trends in the characteristics of patients visiting California emergency departments (EDs) in order to better direct the allocation of acute care resources. DESIGN: A retrospective study. SETTING: We analysed ED utilisation trends between 2005 and 2015 in California using non-public patient data from California's Office of Statewide Health Planning and Development. PARTICIPANTS: We included all ED visits in California from 2005 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: We analysed ED visits and visit rates by age, sex, race/ethnicity, payer and urban/rural trends. We further examined age, sex, race/ethnicity and urban/rural trends within each payer group for a more granular picture of the patient population. Additionally, we looked at the proportion of patients admitted from the ED and distribution of diagnoses. RESULTS: Between 2005 and 2015, the annual number of ED visits increased from 10.2 to 14.2 million in California. ED visit rates increased by 27.8% (p<0.001), with the greatest increases among patients aged 5-19 (37.4%, p<0.001) and 45-64 years (41.1%, p<0.001), non-Hispanic Black and Hispanic patients (56.8% and 48.8%, p<0.001), the uninsured and Medicaid-insured (36.1%, p=0.002; 28.6%, p<0.001) and urban residents (28.3%, p<0.001). The proportion of ED visits resulting in hospitalisation decreased by 18.3%, with decreases across all payer groups. CONCLUSIONS: Our findings reveal an increasing demand for emergency care and may reflect current limitations in accessing care in other parts of the healthcare system. Policymakers may need to recognise the increasingly vital role that EDs are playing in the provision of care and consider ways to incorporate this changing reality into the delivery of health services.

Comparison of qSOFA with current emergency department tools for screening of patients with sepsis for critical illness.

OBJECTIVE: We sought to compare the quick sequential organ failure assessment (qSOFA) to systemic inflammatory response syndrome (SIRS), severe sepsis criteria and lactate levels for their ability to identify ED patients with sepsis with critical illness. METHODS: We conducted this multicenter retrospective cohort study at five US hospitals, enrolling all adult patients admitted to these hospitals from their EDs with infectious disease-related illnesses from 1 January 2016 to 30 April 2016. We abstracted clinical variables for SIRS, severe sepsis and qSOFA scores, using values in the first 6 hours of ED stay. Our primary outcome was critical illness, defined as one or more of the composite outcomes of death, vasopressor use or intensive care unit (ICU) admission within 72 hours of presentation. We determined diagnostic test characteristics for qSOFA scores, SIRS, severe sepsis criteria and lactate level thresholds. MAIN RESULTS: Of 3743 enrolled patients, 512 (13.7%) had the primary composite outcome. The qSOFA scores were ≥1, >2 and 3 in 1839 (49.1%), 626 (16.7%) and 146 (3.9%) patients, respectively; 2202 (58.8%) met SIRS criteria and 1085 (29.0%) met severe sepsis criteria. qSOFA ≥1 and SIRS had similarly high sensitivity [86.1% (95% CI 82.8% to 89.0%) vs 86.7% (95% CI 83.5% to 89.5%)], but qSOFA ≥1 had higher specificity [56.7% (95% CI 55.0% to 58.5%) vs 45.6% (43.9% to 47.3%); mean difference 11.1% (95% CI 8.7% to 13.6%)]. qSOFA ≥2 had higher specificity than severe sepsis criteria [89.1% (88.0% to 90.2%) vs 77.5% (76.0% to 78.9%); mean difference 11.6% (9.8% to 13.4%)]. qSOFA ≥1 had greater sensitivity than a lactate level ≥2 (mean difference 24.6% (19.2% to 29.9%)). CONCLUSION: For patients admitted from the ED with infectious disease diagnoses, qSOFA criteria performed as well or better than SIRS criteria, severe sepsis criteria and lactate levels in predicting critical illness.

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10-7) and suggestive (P < 7.06 × 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and ß-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.

The Body Mass Index of San Francisco Cold-water Swimmers: Comparisons to U.S. National and Local Populations, and Pool Swimmers.

To determine if cold-water swimmers have substantial differences in BMI, which might have a protective effect against heat loss during swims in cold water without wetsuits, and to determine if obesity is more or less prevalent in cold-water swimmers, we compared the body mass index (BMI) values of 103 recreational open-water swimmers (mean age 54.3 ±10.8 years) to data from various population groups. Swimmers swam consistently throughout the winter months, in the San Francisco Bay (water temperature range: 9.6° C [49.3 ° F] to 12.6° C [54.7 ° F]), without wetsuits. After matching for age and sex, the average BMI of cold-water swimmers (25.9 kg/m2) was lower than the corresponding predicted U.S. average BMI (29.2 kg/m2; p<.001), the predicted California state average BMI (28.0 kg/m2; p<.001), and the predicted San Francisco city average BMI (26.6 kg/m2; p=.047). The average BMI value for cold-water swimmers (25.9 kg/m2) was not significantly different from values of North American masters pool swimmers (25.1 kg/m2; p=.15) or international masters pool swimmers (25.3 kg/m2; p=.16). 10.7% of cold-water swimmers were classified as obese (BMI > 30 kg/m2) vs. 35.7%, 25.8%, and 11.8% of the U.S., California, and San Francisco populations, respectively. The lower or similar BMI values of our swimmers suggest that successful recreational swimming in cold water is influenced by factors other than body habitus, such as acclimatization, heat production while swimming, and most importantly, limiting immersion time. The relatively low prevalence of obesity in our swimmers suggests that cold-water swimming could contribute to a healthy lifestyle.

California Sea Lion (Zalophus californianus) and Harbor Seal (Phoca vitulina richardii) Bites and Contact Abrasions in Open-Water Swimmers: A Series of 11 Cases.

OBJECTIVE: To review cases of bites and contact abrasions in open-water swimmers from California sea lions (Zalophus californianus) and harbor seals (Phoca vitulina richardii). METHODS: Open-water swimmers from a San Francisco swimming club were questioned about encounters with pinnipeds (seals and sea lions) that resulted in bites or contact abrasions. When possible, wounds were documented with photographs. Medical follow-up and treatment complications were also reviewed. RESULTS: From October 2011 to December 2014, 11 swimmers reported bites by a sea lion (n = 1), harbor seal (n = 7), or unidentified pinniped (n = 3). Ten of the encounters occurred in San Francisco Bay; 1 occurred in the Eld Inlet, in Puget Sound, near Olympia, WA. None of the swimmers were wearing wetsuits. All bites involved the lower extremities; skin was broken in 4 of 11 bites and antibiotics were prescribed in 3 cases. One swimmer, who was bitten by a harbor seal, also had claw scratches. A treatment failure occurred with amoxicillin/clavulanate in another swimmer who was bitten by an unidentified pinniped; the wound healed subsequently with doxycycline, suggesting an infection with Mycoplasma spp. There were no long-lasting consequences from any of the bites. The majority of cases occurred at low tide, and bumping of the swimmer by the animal before or after a bite was common, but no clear tide or attack pattern was identified. CONCLUSIONS: Bites and contact abrasions from sea lions and harbor seals are reported infrequently in open-water swimmers and typically involve the lower extremities. Because of the risk of Mycoplasma infection, treatment with a tetracycline is recommended in pinniped bites with signs of infection or serious trauma. Attempting to touch or pet sea lions or seals is inadvisable and prohibited by the Marine Mammal Protection Act. Swimmers should leave the water as soon as possible after a bite or encounter.

Physical examination: Mallampati score as an independent predictor of obstructive sleep apnea.

STUDY OBJECTIVE: To assess the clinical usefulness of the Mallampati score in patients with obstructive sleep apnea. Mallampati scoring of the orophyarynx is a simple noninvasive method used to assess the difficulty of endotracheal intubation, but its clinical usefulness has not been validated in patients with sleep-disordered breathing. DESIGN: Prospective multivariate assessment of a predictor variable. SETTING: The UCSF Sleep Disorders Center. PATIENTS OR PARTICIPANTS: One hundred thirty-seven adult patients who were evaluated for possible obstructive sleep apnea. INTERVENTIONS: Prospective determination of the Mallampati score, assessment of other variables for multivariate analysis, and subsequent overnight polysomnography. MEASUREMENTS AND RESULTS: The Mallampati score was an independent predictor of both the presence and severity of obstructive sleep apnea. On average, for every 1-point increase in the Mallampati score, the odds of having obstructive sleep apnea (apnea-hypopnea index> or = 5) increased more than 2-fold (odds ratio [per 1-point increase] = 2.5; 95% confidence interval: 1.2-5.0; p = .01), and the apnea-hypopnea index increased by more than 5 events per hour (coefficient = 5.2; 95% confidence interval: 0.2-10; p = .04). These results were independent of more than 30 variables that reflected airway anatomy, body habitus, symptoms, and medical history. CONCLUSION: Our results indicate that Mallampati scoring is a useful part of the physical examination of patients prior to polysomnography. The independent association between Mallampati score and presence and severity of obstructive sleep apnea suggests that this scoring system will have practical value in clinical settings and prospective studies of sleep-disordered breathing.

Prognostic value of surfactant proteins A and D in patients with acute lung injury.

OBJECTIVE: The primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes. DESIGN: Observational study. SETTING: Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital. PATIENTS: Thirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference. INTERVENTIONS: Undiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients. MEASUREMENTS AND MAIN RESULTS: The concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p = .03) and in patients with an absence of intact alveolar fluid clearance (p =.03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p = .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL; p = .02). CONCLUSIONS: These results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis.

Hypothermia from prolonged immersion: biophysical parameters of a survivor.

We report a case of survival following prolonged immersion and hypothermia. The patient survived for over 9 h in open water, after his vessel capsized and sank in the Pacific Ocean off the coast of Northern California. Water temperature on the day of the sinking was 14.4 degrees C (58.0 degrees F). Although he did have adequate flotation, the patient did not wear a survival suit. On initial physical examination in the Emergency Department (ED), the patient's rectal temperature was 30.0 degrees C (86.0 degrees F). With active rewarming, his temperature returned to normal (37.0 degrees C (98.6 degrees F)) within 5 h. Body fat of the patient was 19.6%, near the 50th percentile for his age (19.0%). Surface/volume ratio of the patient (.0228 m(2)/L) was 19% smaller than a predicted average (.0282 m(2)/L). We believe that the patient's large body habitus contributed to survival and that surface/volume ratio was likely the biophysical variable most closely associated with decreased cooling.

Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure.

OBJECTIVE: Experimental studies demonstrate that beta-adrenergic agonists markedly stimulate alveolar fluid clearance if concentrations of 10(-6) M are achieved in alveolar fluid. However, no studies have determined whether aerosolized beta-adrenergic agonists are delivered to the distal air spaces of the lung in therapeutic concentrations in patients with pulmonary edema. DESIGN AND SETTING: This retrospective study measured albuterol levels in the pulmonary edema fluid and plasma from mechanically ventilated patients with pulmonary edema from a hydrostatic mechanism ( n=10) or from acute lung injury ( n=12). MEASUREMENTS AND RESULTS: After a total aerosolized albuterol dose of 4.2+/-3.2 mg in the prior 6 h the median pulmonary edema fluid albuterol level was 1,250 ng/ml (10(-6) M) in patients with hydrostatic pulmonary edema; after 3.5+/-2.6 mg the figure was 1,240 ng/ml (10(-6) M) in patients with pulmonary edema from acute lung injury. Plasma albuterol levels were much lower, with a median of 5.2 ng/ml (0.01 x 10(-6) M) in patients with hydrostatic pulmonary edema and 3.1 ng/ml (0.01 x 10(-6) M) in patients with pulmonary edema from acute lung injury. CONCLUSIONS: These results provide the first evidence that levels of beta-adrenergic agonists that are physiologically efficacious in experimental models can be achieved with conventional delivery systems in ventilated, critically ill patients with acute respiratory failure from pulmonary edema.

Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.

BACKGROUND: No single pulmonary-specific variable, including the severity of hypoxemia, has been found to predict the risk of death independently when measured early in the course of the acute respiratory distress syndrome. Because an increase in the pulmonary dead-space fraction has been described in observational studies of the syndrome, we systematically measured the dead-space fraction early in the course of the illness and evaluated its potential association with the risk of death. METHODS: The dead-space fraction was prospectively measured in 179 intubated patients, a mean (+/-SD) of 10.9+/-7.4 hours after the acute respiratory distress syndrome had developed. Additional clinical and physiological variables were analyzed with the use of multiple logistic regression. The study outcome was mortality before hospital discharge. RESULTS: The mean dead-space fraction was markedly elevated (0.58+/-0.09) early in the course of the acute respiratory distress syndrome and was higher among patients who died than among those who survived (0.63+/-0.10 vs. 0.54+/-0.09, P<0.001). The dead-space fraction was an independent risk factor for death: for every 0.05 increase, the odds of death increased by 45 percent (odds ratio, 1.45; 95 percent confidence interval, 1.15 to 1.83; P=0.002). The only other independent predictors of an increased risk of death were the Simplified Acute Physiology Score II, an indicator of the severity of illness (odds ratio, 1.06; 95 percent confidence interval, 1.03 to 1.08; P<0.001) and quasistatic respiratory compliance (odds ratio, 1.06; 95 percent confidence interval, 1.01 to 1.10; P=0.01). CONCLUSIONS: Increased dead-space fraction is a feature of the early phase of the acute respiratory distress syndrome. Elevated values are associated with an increased risk of death.

Activity of pulmonary edema fluid interleukin-8 bound to alpha(2)-macroglobulin in patients with acute lung injury.

The formation of alpha(2)-macroglobulin (alpha(2)-M)/interleukin-8 (IL-8) complexes may influence the biological activity of IL-8 and the quantitative assessment of IL-8 activity. Therefore, in this study, concentrations of free IL-8 and IL-8 complexes with alpha(2)-M were measured in pulmonary edema fluid samples from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and compared with control patients with hydrostatic pulmonary edema. Patients with ALI/ARDS had significantly higher concentrations of alpha(2)-M (P < 0.01) as well as alpha(2)-M/IL-8 complexes (P < 0.05). Because a substantial amount of IL-8 is complexed to alpha(2)-M, standard assays of free IL-8 may significantly underestimate the concentration of biologically active IL-8 in the distal air spaces of patients with ALI/ARDS. Furthermore, IL-8 bound to alpha(2)-M retained its biological activity, and this fraction of IL-8 was protected from proteolytic degradation. Thus complex formation may modulate the acute inflammatory process in the lung.