Neil R. MacIntyre

Standardisation of spirometry

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 2 in this Series [1]: #F13

Interpretative strategies for lung function tests

SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 5 in this Series This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes. Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity ( D L,CO) and lung volumes. The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and D L,CO measurement have been considered in other documents published in this series of Task Force reports 1–4 and in the American Thoracic Society (ATS) interpretative strategies document 5. An interpretation begins with a review and comment on test quality. Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the direction and magnitude of the potential errors. Omitting the quality review and relying only on numerical results for clinical decision making is a common mistake, which is more easily made by those who are dependent upon computer interpretations. Once quality has been assured, the next steps involve a series of comparisons 6 that include comparisons of test results with reference values based on healthy subjects 5, comparisons with known disease or abnormal physiological patterns ( i.e. obstruction and restriction), and comparisons with self, a rather formal term for evaluating change in an individual patient. A final step in the lung function report is to answer the clinical question that prompted the test. Poor choices made during these preparatory steps increase the risk of misclassification, i.e. a falsely negative or falsely positive interpretation for a lung function abnormality or a change …

Standardisation of the measurement of lung volumes

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 3 in this Series [1]: #F7

Standardisation of the single-breath determination of carbon monoxide uptake in the lung

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 4 in this Series [1]: #F4

General considerations for lung function testing.

SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 1 in this Series ⇓In preparing the joint statements on lung function testing for the American Thoracic Society (ATS) and the European Respiratory Society (ERS), it was agreed by the working party that the format of the statements should be modified so that they were easier to use by both technical and clinical staff. This statement contains details about procedures that are common for many methods of lung function testing and, hence, are presented on their own. A list of abbreviations used in all the documents is also included as part of this statement. All terms and abbreviations used here are based on a report of the American College of Chest Physicians/ATS Joint Committee on Pulmonary Nomenclature 1. The metrology definitions agreed by the International Standards Organization (ISO) are recommended 2 and some important terms are defined as follows. Accuracy is the closeness of agreement between the result of a measurement and the conventional true value. Repeatability is the closeness of agreement between the results of successive measurements of the same item carried out, subject to all of the following conditions: same method, same observer, same instrument, same location, same condition of use, and repeated over a short space of time. In previous documents, the term reproducibility was used in this context, and this represents a change towards bringing this document in line with the ISO. Reproducibility is the closeness of agreement of the results of successive measurements of the same item where the individual measurements are carried out with changed conditions, such as: method of measurement, observer, instrument, location, conditions of use, and time. Thus, if a technician tests a subject several times, this is looking at the …

The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States.

ObjectiveTo quantify the incidence of anemia and red blood cell (RBC) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes. DesignProspective, multiple center, observational cohort study of intensive care unit (ICU) patients in the United States. Enrollment period was from August 2000 to April 2001. Patients were enrolled within 48 hrs of ICU admission. Patient follow-up was for 30 days, hospital discharge, or death, whichever occurred first. SettingA total of 284 ICUs (medical, surgical, or medical-surgical) in 213 hospitals participated in the study. PatientsA total of 4,892 patients were enrolled in the study. Measurements and Main ResultsThe mean hemoglobin level at baseline was 11.0 ± 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study. Overall, 44% of patients received one or more RBC units while in the ICU (mean, 4.6 ± 4.9 units). The mean pretransfusion hemoglobin was 8.6 ± 1.7 g/dL. The mean time to first ICU transfusion was 2.3 ± 3.7 days. More RBC transfusions were given in study week 1; however, in subsequent weeks, subjects received one to two RBC units per week while in the ICU. The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality. Patients who received transfusions also had more total complications and were more likely to experience a complication. Baseline hemoglobin was related to the number of RBC transfusions, but it was not an independent predictor of length of stay or mortality. However, a nadir hemoglobin level of <9 g/dL was a predictor of increased mortality and length of stay. ConclusionsAnemia is common in the critically ill and results in a large number of RBC transfusions. Transfusion practice has changed little during the past decade. The number of RBC units transfused is an independent predictor of worse clinical outcome.

An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results. Technical Standard document: standard operating procedures for the 6MWT, ISWT and ESWT in chronic respiratory disease http://ow.ly/Bq2B9

A second large controlled clinical study of E5, a monoclonal antibody to endotoxin : results of a prospective, multicenter, randomized, controlled trial

OBJECTIVE To evaluate the safety and efficacy of E5, a murine, monoclonal antibody directed against endotoxin, in the treatment of patients with Gram-negative sepsis. DESIGN A multicenter, randomized, double-blind, placebo-controlled trial. SETTING Fifty-three hospitals across the United States, including university medical centers, Veterans Affairs Medical Centers, and community hospitals. PATIENTS 847 patients were randomized into this study. Enrolled patients met criteria for three conditions: a) known or suspected Gram-negative infection; b) clinical evidence of sepsis; and c) signs of end-organ dysfunction. Patients with refractory shock were excluded from the study. INTERVENTIONS Two doses of E5 (2 mg/kg/day by intravenous infusion 24 hrs apart), or placebo that was identical in appearance were administered. In addition, all patients received standard supportive therapy and broad-spectrum antibiotics. MEASUREMENTS AND MAIN RESULTS The primary end point was mortality over 30 days. Secondary outcome measures included the resolution and prevention of organ failure in the same two populations. Additionally, the safety of E5 was evaluated. There was no significant improvement in survival over 30 days among patients with Gram-negative sepsis who received E5 compared with those patients who received placebo (n = 530; p = .21). In addition, E5 did not improve survival for patients with Gram-negative sepsis and organ failure (n = 139; p = .3). However, a significantly greater percentage of patients with Gram-negative sepsis experienced resolution of major organ failure if they received E5, compared with those patients who received placebo (n = 139; 48% E5 vs. 25% placebo; p = .005). This result extended to all patients who entered the study with one or more major organ failures, regardless of the etiology of the infection (n = 225; 41% E5 vs. 27% placebo; p = .024). E5 also provided protection against the development of some organ failures, but significant prevention was only observed for adult respiratory distress syndrome (p = .007) and central nervous system dysfunction (p = .050). Hypersensitivity reactions attributable to E5 occurred in 2.6% of patients. An asymptomatic antibody response occurred in 44% of the E5-treated patients and in 12% of the patients who received placebo. CONCLUSIONS In this study, E5 did not reduce mortality in nonshock patients with Gram-negative sepsis whether or not those patients also had organ failure. However, E5 did result in greater resolution of organ failure in patients with Gram-negative sepsis. This benefit extended to those patients with suspected Gram-negative etiology. This finding is important because patients with suspected Gram-negative sepsis and organ failure can be identified without waiting for culture results. In addition, E5 resulted in the prevention of adult respiratory distress syndrome and central nervous system organ failure. However, more studies are needed to determine if this result can be extended to organ failure in general. E5 is safe as a treatment for patients with Gram-negative sepsis.

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.

ObjectivePositive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. DesignProspective, randomized, crossover study. SettingThirty-four intensive care units at 19 hospitals. PatientsSeventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 ± 3.0 cm H2O and 0.39 ± 0.10, respectively (mean ± sd). InterventionsWe conducted RMs by applying continuous positive airway pressure of 35–40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. Measurements and Main ResultsResponses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 ± 0.2 vs. 0.6 ± 0.3 %, mean ± sem, p < .01). Systolic blood pressure decreased more within 10 mins after RMs (9.4 ± 1.1 vs. 3.1 ± 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. ConclusionsIn ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.

Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

Objective To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design A prospective, randomized, double-blind, placebo-controlled, multicenter study. Setting Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network. Patients A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group). Interventions Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing. Measurements and Main Results The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure–free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo. Conclusions In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.