Roy T. McKay

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 …

Efficacy and safety of sirolimus in lymphangioleiomyomatosis

BACKGROUND Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. METHODS We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV(1)). RESULTS During the treatment period, the FEV(1) slope was -12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV(1) during the treatment period was 153 ml, or approximately 11% of the mean FEV(1) at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups. CONCLUSIONS In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES ClinicalTrials.gov number, NCT00414648.).

Performance of an N95 filtering facepiece particulate respirator and a surgical mask during human breathing: two pathways for particle penetration.

The protection level offered by filtering facepiece particulate respirators and face masks is defined by the percentage of ambient particles penetrating inside the protection device. There are two penetration pathways: (1) through the faceseal leakage, and the (2) filter medium. This study aimed at differentiating the contributions of these two pathways for particles in the size range of 0.03–1 μm under actual breathing conditions. One N95 filtering facepiece respirator and one surgical mask commonly used in health care environments were tested on 25 subjects (matching the latest National Institute for Occupational Safety and Health fit testing panel) as the subjects performed conventional fit test exercises. The respirator and the mask were also tested with breathing manikins that precisely mimicked the prerecorded breathing patterns of the tested subjects. The penetration data obtained in the human subject- and manikin-based tests were compared for different particle sizes and breathing patterns. Overall, 5250 particle size- and exercise-specific penetration values were determined. For each value, the faceseal leakage-to-filter ratio was calculated to quantify the relative contributions of the two penetration pathways. The number of particles penetrating through the faceseal leakage of the tested respirator/mask far exceeded the number of those penetrating through the filter medium. For the N95 respirator, the excess was (on average) by an order of magnitude and significantly increased with an increase in particle size (p < 0.001): ∼7-fold greater for 0.04 μm, ∼10-fold for 0.1 μm, and ∼20-fold for 1 μm. For the surgical mask, the faceseal leakage-to-filter ratio ranged from 4.8 to 5.8 and was not significantly affected by the particle size for the tested submicrometer fraction. Facial/body movement had a pronounced effect on the relative contribution of the two penetration pathways. Breathing intensity and facial dimensions showed some (although limited) influence. Because most of the penetrated particles entered through the faceseal, the priority in respirator/mask development should be shifted from improving the efficiency of the filter medium to establishing a better fit that would eliminate or minimize faceseal leakage.

Guidelines for bronchoprovocation on the investigation of occupational asthma: Report of the Subcommittee on Bronchoprovocation for Occupational Asthma

Asthma can be induced or exacerbated at work by several means. Four work-related disorders, characterized by airflow obstruction and airway hyperresponsivene ss, have been described. These include: occupational asthma, byssinosis, the reactive airways dysfunction syndrome, and variable airflow obstruction caused by irritant substances. This committee has elected to focus only on the topic of occupational asthma, which is defined as asthma that is either induced or exacerbated by exposure to a specific (as opposed to an irritant) agent found at work. The Committee has decided to exclude discussion of other causes of asthmatic exacerbations at work, which does not mean that these conditions are not important. It may also, as discussed in other sections of this report, be quite difficult to distinguish an irritant effect from a specific bronchospastic response. A preexisting history of asthma before exposure to the offending agent does not preclude the diagnosis of occupational asthma.

Aerosol penetration and leakae characteristics of masks used in the health care industry

BACKGROUND Historically, surgical masks have been worn to protect patients from being infected by large, pathogen-containing aerosol droplets emitted by health care personnel. Today, emphasis has shifted from solely protecting the patient to protecting the health care worker as well. As a result of new procedures used in operating rooms and clinical areas, aerosolized hazardous agents in the submicrometer size range are being produced, posing a potential threat to health care workers. METHODS Eight surgical masks were tested for aerosol particle penetration through their filter media and through induced face-seal leaks. RESULTS The percentage of filter penetration ranged from 20% to nearly 100% for submicrometer-sized particles. In comparison, a dust-mist-fume respirator used in industrial settings had significantly less penetration through its filter medium. When the surgical masks had artificially induced face-seal leaks, the concentration of submicrometer-sized particles inside the mask increased slightly; in contrast, the more protective dust-mist-fume respirator showed a fourfold increase in aerosol penetration into the mask with an artificial leak 4 mm in diameter. CONCLUSION We conclude that the protection provided by surgical masks may be insufficient in environments containing potentially hazardous submicrometer-sized aerosols.

Respiratory protection provided by N95 filtering facepiece respirators against airborne dust and microorganisms in agricultural farms.

A new system was used to determine the workplace protection factors (WPF) for dust and bioaerosols in agricultural environments. The field study was performed with a subject wearing an N95 filtering facepiece respirator while performing animal feeding, grain harvesting and unloading, and routine investigation of facilities. As expected, the geometric means (GM) of the WPFs increased with increasing particle size ranging from 21 for 0.7–1 μm particles to 270 for 5–10 μm particles (p < 0.001). The WPF for total culturable fungi (GM = 35) was significantly greater than for total culturable bacteria (GM = 9) (p = 0.01). Among the different microorganism groups, the WPFs of Cladosporium, culturable fungi, and total fungi were significantly correlated with the WPFs of particles of the same sizes. As compared with the WPFs for dust particles, the WPFs for bioaerosols were found more frequently below 10, which is a recommended assigned protection factor (APF) for N95 filtering facepiece respirators. More than 50% of the WPFs for microorganisms (mean aerodynamic diameter < 5 μm) were less than the proposed APF of 10. Even lower WPFs were calculated after correcting for dead space and lung deposition. Thus, the APF of 10 for N95 filtering facepiece respirators seems inadequate against microorganisms (mean aerodynamic size < 5 μm). These results provide useful pilot data to establish guidelines for respiratory protection against airborne dust and microorganisms on agricultural farms. The method is a promising tool for further epidemiological and intervention studies in agricultural and other similar occupational and nonoccupational environments.