Jeffrey J. Pretto

Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial

Obesity and asthma are associated conditions; however, the mechanisms linking the two remain unclear. Few studies have examined the effects of weight loss on inflammation and clinical outcomes in obese–asthma.

A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia

Background Patients with chronic obstructive pulmonary disease (COPD) who are not severely hypoxaemic at rest may experience significant breathlessness on exertion, and ambulatory oxygen is often prescribed in this circumstance despite a lack of conclusive evidence for benefit. This study aimed to determine whether such patients benefit from domiciliary ambulatory oxygen and, if so, which factors may be associated with benefit. Methods This was a 12 week, parallel, double-blinded, randomised, placebo-controlled trial of cylinder air versus cylinder oxygen, provided at 6 l/min intranasally, for use during any activity provoking breathlessness. Patients underwent baseline measurements of arterial blood gases and lung function. Outcome measures assessed dyspnoea, health-related quality of life, mood disturbance, functional status and cylinder utilisation. Data were analysed on an intention-to-treat basis, p≤0.05. Results 143 subjects (44 female), mean±SD age 71.8±9.8 years, forced expiratory volume in 1 s (FEV1)1.16±0.51 lites, Pao2 9.5±1.1 kPa (71.4±8.5 mm Hg) were randomised, including 50 patients with exertional desaturation to ≤88%. No significant differences in any outcome were found between groups receiving air or oxygen. Statistically significant but clinically small improvements in dyspnoea and depression were observed in the whole study group over the 12 weeks of the study. Conclusion In breathless patients with COPD who do not have severe resting hypoxaemia, domiciliary ambulatory oxygen confers no benefits in terms of dyspnoea, quality of life or function. Exertional desaturation is not predictive of outcome. Intranasal gas (either air or oxygen) may provide a placebo benefit. Clinical trial number ACTRN12605000457640.

Implications of adopting the Global Lungs Initiative 2012 all-age reference equations for spirometry

The aim of this study was to determine the diagnostic and interpretative consequences of adopting the Global Lungs Initiative (GLI) 2012 spirometric prediction equations. We assessed spirometric records from 17 572 subjects (49.5% females), aged 18–85 years, from hospitals in Australia and Poland. We calculated predicted forced expiratory volume in 1 s (FEV1), forced expiratory volume (FVC), FEV1/FVC and lower limits of normal (LLN) using European Community for Steel and Coal (ECSC), National Health and Nutrition Examination Survey (NHANES) III and GLI 2012 equations. Obstruction was defined as FEV1/FVC<LLN and a restrictive pattern as FEV1/FVC>LLN and FVC<LLN. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher was defined as FEV1/FVC <0.70 and FEV1 <80% pred. GLI 2012 equations produce similar predicted values for FEV1 and FVC compared with NHANES, but produce larger values than ECSC. Differences in the LLN lead to an important increase in the prevalence rate of a low FVC compared to ECSC, and a significant decrease compared to NHANES prediction equations. Adopting GLI 2012 equations has small effects on the prevalence rate of airway obstruction. GOLD stages 2–4 lead to >20% underdiagnosis of airway obstruction up to the age of 55 years and to 16–23% overdiagnosis in older subjects. GLI 2012 equations increase the prevalence of a “restrictive spirometric pattern” compared to ECSC but decrease it compared to NHANES. Adopting the Global Lung Initiative 2012 prediction equations will have small effects on spirometric rates of detection http://ow.ly/nrZxe

Head-down tilt and manual hyperinflation enhance sputum clearance in patients who are intubated and ventilated

The purpose of this prospective randomised cross-over study was to measure peak expiratory flow rates during manual hyperinflation and to determine if the addition of a head-down tilt to physiotherapy treatment increased sputum production in patients who are intubated and ventilated. Twenty patients who were intubated, ventilated and haemodynamically stable were randomised to a sequence of physiotherapy treatment in a flat side-lying or a head-down tilt position. Peak expiratory flow rates were measured for each breath during manual hyperinflation using a Vitalograph peak flow meter. Sputum wet weight was collected for each treatment position and static pulmonary compliance was measured before and immediately following physiotherapy treatment. There was a significant increase in peak expiratory flow (p < 0.001) and sputum production (p = 0.008) in the head-down tilt position. The mean difference and 95% confidence intervals for expiratory flow were 0.17 (0.15 to 0.19) l/sec and for the wet weight of sputum 1.97 (0.84 to 3.10) g. The peak expiratory flow rate was sufficient to produce annular flow in both flat side-lying (1.97 +/- 0.09) l/sec and in the head-down tilt position (2.14 +/- 0.08) l/sec. Static pulmonary compliance improved significantly following physiotherapy treatment (p = 0.003). The mean difference and 95% confidence intervals pre- and post-treatment for static pulmonary compliance were 5.18 (2.14 to 8.22) ml/cmH(2)O. The results suggest that addition of a head-down tilt to physiotherapy treatment, including manual hyperinflation, in patients who are intubated and ventilated, increases sputum production and improves peak expiratory flow.

Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making

The aim of this study was to determine the added value of measuring the forced expiratory flow at 25–75% of forced vital capacity (FVC) (FEF25–75%) and flow when 75% of FVC has been exhaled (FEF75%) over and above the measurement of the forced expiratory volume in 1 s (FEV1), FVC and FEV1/FVC ratio. We used spirometric measurements of FEV1, FVC and FEF25–75% from 11 654 white males and 11 113 white females, aged 3–94 years, routinely tested in the pulmonary function laboratories of four tertiary hospitals. FEF75% was available in 8254 males and 7407 females. Predicted values and lower limits of normal, defined as the fifth percentile, were calculated for FEV1, FVC, FEV1/FVC ratio, FEF25–75% and FEF75% using prediction equations from the Global Lung Function Initiative. There was very little discordance in classifying test results. FEF25–75% and FEF75% were below the normal range in only 2.75% and 1.29% of cases, respectively, whereas FEV1, FVC and FEV1/FVC ratio were within normal limits. Airways obstruction went undetected by FEF25–75% in 2.9% of cases and by FEF75% in 12.3% of cases. Maximum mid-expiratory flow and flow towards the end of the forced expiratory manoeuvre do not contribute usefully to clinical decision making over and above information from FEV1, FVC and FEV1/FVC ratio. Forced expiratory flow measurements do not contribute usefully to clinical decision making http://ow.ly/t6Xz1

Grading the severity of airways obstruction: new wine in new bottles

The objective of this study was to redesign the current grading of obstructive lung disease so that it is clinically relevant and free of biases related to age, height, sex and ethnic group. Spirometric records from 17 880 subjects (50.4% female) from hospitals in Australia and Poland, and 21 191 records (53.0% female) from two epidemiological studies (age range 18–95 years) were analysed. We adopted the American Thoracic Society(ATS)/European Respiratory Society (ERS) criteria for airways obstruction based on an forced expiratory volume in 1 s (FEV1)/(forced) vital capacity ((F)VC) ratio below the fifth percentile and graded the severity of pulmonary function impairment using z-scores for FEV1, which signify how many standard deviations a result is from the mean predicted value. Using the lower limit of normal for FEV1/(F)VC and z-scores for FEV1 of -2, -2.5, -3 and -4 to delineate severity grades of airflow limitation leads to close agreement with ATS/ERS severity classifications and removes age, sex and height related bias. The new classification system is simple, easily memorised and clinically valid. It retains previously established associations with clinical outcomes and avoids biases due to the use of per cent predicted FEV1. Combined with the Global Lung Function prediction equations it provides a worldwide diagnostic standard, free of bias due to age, height, sex and ethnic group. Using FEV1 z-scores to classify severity of airways obstruction is clinically valid and overcomes bias inherent in % pred http://ow.ly/pRyGI

Pilot Study of Remote Telemonitoring in COPD

BACKGROUND Remote in-home monitoring (RM) of symptoms and physiological variables may allow early detection and treatment of exacerbations of chronic obstructive pulmonary disease (COPD). It is unclear whether RM improves patient outcomes or healthcare resource utilization. This study determined whether RM is feasible in patients with COPD and if RM reduces hospital admissions or length of stay (LOS) or improves health-related quality of life (HRQOL). SUBJECTS AND METHODS Forty-four patients were randomized to standard best practice care (SBP) (n=22) or SBP+RM (n=22). RM involved daily recording of physiological variables, symptoms, and medication usage. RESULTS There were no differences (mean±SD, SBP versus SBP+RM) in age (68±8 versus 70±9 years), gender (male:female 10:12 in both groups), or previous computer familiarity (59% versus 50%) between groups. The SBP group had a lower forced expiratory volume in 1 s (0.66±0.24 versus 0.91±0.34 L, p<0.01) and more current smokers (six versus none, p<0.05). There were no differences in number of COPD-related admissions/year (1.5±1.8 versus 1.3±1.7, p=0.76), COPD-related LOS days/year (15.6±19.4 versus 11.4±19.6, p=0.66), total admissions/year (2.2±2.1 versus 2.0±2.3, p=0.86), total LOS days/year (22.1±29.9 versus 21.6±30.4, p=0.88), or HRQOL between the two groups. CONCLUSIONS The addition of RM to SBP was feasible but did not reduce healthcare utilization or improve quality of life in this group of patients already receiving comprehensive respiratory care.

Relationship between body composition, inflammation and lung function in overweight and obese asthma

BackgroundThe obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma.MethodsOverweight and obese (BMI 28-40 kg/m2) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers.ResultsIn females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males.ConclusionsThis study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.

Effect of Singing on Respiratory Function, Voice, and Mood After Quadriplegia: A Randomized Controlled Trial

OBJECTIVE To explore the effects of singing training on respiratory function, voice, mood, and quality of life for people with quadriplegia. DESIGN Randomized controlled trial. SETTING Large, university-affiliated public hospital, Victoria, Australia. PARTICIPANTS Participants (N=24) with chronic quadriplegia (C4-8, American Spinal Injury Association grades A and B). INTERVENTIONS The experimental group (n=13) received group singing training 3 times weekly for 12 weeks. The control group (n=11) received group music appreciation and relaxation for 12 weeks. Assessments were conducted pre, mid-, immediately post-, and 6-months postintervention. MAIN OUTCOME MEASURES Standard respiratory function testing, surface electromyographic activity from accessory respiratory muscles, sound pressure levels during vocal tasks, assessments of voice quality (Perceptual Voice Profile, Multidimensional Voice Profile), and Voice Handicap Index, Profile of Mood States, and Assessment of Quality of Life instruments. RESULTS The singing group increased projected speech intensity (P=.028) and maximum phonation length (P=.007) significantly more than the control group. Trends for improvements in respiratory function, muscle strength, and recruitment were also evident for the singing group. These effects were limited by small sample sizes with large intersubject variability. Both groups demonstrated an improvement in mood (P=.002), which was maintained in the music appreciation and relaxation group after 6 months (P=.017). CONCLUSIONS Group music therapy can have a positive effect on not only physical outcomes, but also can improve mood, energy, social participation, and quality of life for an at-risk population, such as those with quadriplegia. Specific singing therapy can augment these general improvements by improving vocal intensity.

Successful treatment of Langerhans cell histiocytosis with 2-chlorodeoxyadenosine

Abstract:  Langerhans cell histiocytosis (LCH) is a rare disorder which frequently involves the lungs of affected adults. Recent evidence suggests it is a clonal neoplastic disorder. Prognosis in this disease is variable, but in its multisystem form or when associated with progressive respiratory dysfunction, prognosis is poor. Recent case reports and a phase II trial of the antimonocyte drug 2‐chlorodeoxyadenosine (2CDA) have described success in treating LCH. We used 2CDA to treat a young Australian man with LCH involving lungs and bone. A complete symptomatic remission was achieved with no evidence of recurrence some 5 years after completion of chemotherapy.