Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD). Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate. Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found. Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy. (AU)

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data.

INTRODUCTION: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD). METHODS: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate. RESULTS: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found. CONCLUSION: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy.

Missed diagnosis or misdiagnosis: how often do hospitalised patients with a diagnosis of chronic obstructive pulmonary disease have spirometry that supports the diagnosis?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common clinical diagnoses among hospital inpatients. Diagnosis requires the demonstration of post-bronchodilator airflow obstruction. However, it is uncertain how often spirometry results are available at the time a diagnostic label of COPD is applied. AIMS: To identify how frequently spirometry results were available following an inpatient admission with a clinical diagnosis of COPD, and to determine how often the available spirometry results supported a clinical diagnosis of COPD. Inhaler prescription, at discharge, was also evaluated to determine one of the potential implications of diagnostic inaccuracy. METHODS: A single-centre retrospective observational study was undertaken at a 400-bed metropolitan health service between October 2016 and March 2018. RESULTS: A total of 2239 inpatient separations occurred in 1469 individuals who had a clinical diagnosis of COPD during the study. Spirometry results were not available in 43.6% (n = 641) of those with a diagnosis of COPD. A further 19.7% (n = 289) had spirometry results available at the time of admission that did not demonstrate fixed airflow obstruction. The available prescribing data (n = 443) demonstrated that inhaled medications were prescribed in a similar pattern, regardless of the availability of spirometry or whether the results supported a clinical diagnosis of COPD. CONCLUSIONS: Inpatients with a clinical diagnosis of COPD frequently did not have supportive spirometry results that confirmed the diagnosis or had results inconsistent with COPD. Misdiagnosis and inappropriate prescribing require further attention to improve the quality of care in this setting.

Diaphragm dysfunction: a comprehensive review from diagnosis to management.

Although the diaphragm represents a critical component of the respiratory pump, the clinical presentations of diaphragm dysfunction are often non-specific and can be mistaken for other more common causes of dyspnoea. While acute bilateral diaphragm dysfunction typically presents dramatically, progressive diaphragm dysfunction associated with neuromuscular disorders and unilateral hemidiaphragm dysfunction may be identified incidentally or by recognising subtle associated symptoms. Diaphragm dysfunction should be considered in individuals with unexplained dyspnoea, restrictive respiratory function tests or abnormal diaphragm position on plain chest imaging. A higher index of suspicion should occur for individuals with profound orthopnoea, those who have undergone procedures in proximity to the phrenic nerve(s) or those with co-morbid conditions that are associated with diaphragm dysfunction, particularly neuromuscular disorders. A systematic approach to the evaluation of diaphragm function using non-invasive diagnostic techniques such as respiratory function testing and diaphragm imaging can often confirm a diagnosis. Neurophysiological assessment may confirm diaphragm dysfunction and assist in identifying an underlying cause. Identifying those with or at risk of respiratory failure can allow institution of respiratory support, while specific cases may also benefit from surgical plication or phrenic nerve pacing techniques.

Measuring Adherence to Long-Term Noninvasive Ventilation.

BACKGROUND: Obtaining benefits from long-term noninvasive ventilation (NIV) relies on achieving adequate adherence to treatment. Reported adherence to NIV is variable and could be influenced by high-volume users and attrition of nonusers and those who die. This observational study aimed to describe patterns of use and adherence rates in new unselected users of NIV. METHODS: All adults (> 18 y old) commencing long-term NIV were consecutively enrolled and followed for 6 months. Ventilator data were manually downloaded from devices and usage (minutes per day) was collected. Subjects were categorized into adherent users (≥ 4 h/d) and nonadherent users (< 4 h/d). RESULTS: Data were obtained from 86 subjects. Most (65%) had motor neuron disease, and most commenced NIV in an out-patient setting (72%). At one month after NIV implementation, overall average daily use was 302.1 min/d and categorical adherence was 57%. At 6 months or prior to death, overall average daily use increased (388.7 min/d), but categorical adherence was similar (62%). The majority of subjects (84%) remained in the same adherence category from their first month to their sixth month of use or death. Individuals with motor neuron disease demonstrated significantly lower rates of adherence compared to the rest of the cohort at 1 month (48% vs 73%, P = .03). In those who died within the study period (n = 19, all with motor neuron disease), this difference persisted to death (42% at death vs 73% at 6 months, P = .032). CONCLUSIONS: Average daily usage may conceal true prevalence of adherence or nonadherence to NIV within a population. Reporting both average daily use data and categorical adherence rates (using a threshold of 4 h/d) may improve transparency of reported outcomes from clinical trials and identifies a therapeutic target for home mechanical ventilation services for quality improvement.

Improving access to ward-based respiratory failure management: a case study in the development of a respiratory care unit at an Australian metropolitan health service.

This case study describes the implementation of a ward-based respiratory care unit to improve access to specialised respiratory failure management at an Australian metropolitan health service. Using a case study approach, we describe the conception, development and implementation of a respiratory care unit within a previously inexperienced ward. Key barriers and facilitators are explored and the importance of a safety culture and an aspiration for continuous quality improvement are detailed. Three key aspects of implementation were identified: physical environment, expertise and governance. Continuous review of clinical and quality data was also considered critical to success. Stakeholder engagement was identified as both a barrier and facilitator to successful implementation. Early success was demonstrated through increased utilisation of respiratory interventions but with less utilisation of the intensive care unit and no apparent deterioration in clinical outcomes. Successful implementation of ward-based management of respiratory failure can be undertaken within non-tertiary settings but requires a comprehensive plan. Essential aspects include the support of clinical champions, early and continuous stakeholder engagement and an aspirational culture of safety and continuous quality improvement.What is known about the topic?Non-invasive ventilation and high-flow oxygen therapy are now established as key treatments in the management of acute respiratory failure. Access to these treatments is often limited to critical care locations (emergency department, intensive care unit (ICU) and operating theatre), but ward-based use can be safe and effective when applied with appropriate clinical policies, expertise and staffing.What does this paper add?This report describes the successful and rapid development of a specialised respiratory care unit within an inexperienced ward at an Australian metropolitan health service. Prior to development of the unit, the health service only provided non-invasive ventilation and high-flow oxygen therapy within critical care locations. Successful implementation was associated with increased utilisation of these therapies with significantly less ICU utilisation and no apparent deterioration in outcomes.What are the implications for practitioners?An explanation of a model for implementation is provided that may help health services improve access to complex respiratory failure management outside of critical care locations. Key factors in the success of the model are identified and examined.

Typical within and between person variability in non-invasive ventilator derived variables among clinically stable, long-term users.

BACKGROUND: Despite increasing capacity to remotely monitor non-invasive ventilation (NIV), how remote data varies from day to day and person to person is poorly described. METHODS: Single-centre, 2-month, prospective study of clinically stable adults on long-term NIV which aimed to document NIV-device variability. Participants were switched to a ventilator with tele-monitoring capabilities. Ventilation settings and masking were not altered. Raw, extensible markup language data files were provided directly from Philips Respironics (EncoreAnywhere). A nested analysis of variance was conducted on each ventilator variable to apportion the relative variation between and within participants. RESULTS: Twenty-nine people were recruited (four withdrew, one had insufficient data for analyses; 1364 days of data). Mean age was 54.0 years (SD 18.4), 58.3% male with body mass index of 37.0 kg/m2 (13.7). Mean adherence was 8.53 (2.23) hours/day and all participants had adherence >4 hours/day. Variance in ventilator-derived indices was predominantly driven by differences between participants; usage (61% between vs 39% within), Apnoea-Hypopnoea Index (71% vs 29%), unintentional (64% vs 36%) and total leak (83% vs 17%), tidal volume (93% vs 7%), minute ventilation (92% vs 8%), respiratory rate (92% vs 8%) and percentage of triggered breaths (93% vs 7%). INTERPRETATION: In this clinically stable cohort, all device-derived indices were more varied between users than the day-to-day variation within individuals. We speculate that normative ranges and thresholds for clinical intervention need to be individualised, and further research is necessary to determine the clinically important relationships between clinician targets for therapy and patient-reported outcomes.

Randomised controlled trial of polysomnographic titration of noninvasive ventilation.

Noninvasive ventilation (NIV) settings determined during wakefulness may produce patient-ventilator asynchrony (PVA) during sleep, causing sleep disruption and limiting tolerance. This study investigated whether NIV titrated with polysomnography (PSG) is associated with less PVA and sleep disruption than therapy titrated during daytime alone.Treatment-naive individuals referred for NIV were randomised to control (daytime titration followed by sham polysomnographic titration) or PSG (daytime titration followed by polysomnographic titration) groups. Primary outcomes were PVA and arousal indices on PSG at 10 weeks. Secondary outcomes included adherence, gas exchange, symptoms and health-related quality of life (HRQoL).In total, 60 participants were randomised. Most (88.3%) had a neuromuscular disorder and respiratory muscle weakness but minor derangements in daytime arterial blood gases. PVA events were less frequent in those undergoing polysomnographic titration (median (interquartile range (IQR)): PSG 25.7 (12-68) events·h-1 versus control 41.0 (28-182) events·h-1; p=0.046), but arousals were not significantly different (median (IQR): PSG 11.4 (9-19) arousals·h-1 versus control 14.6 (11-19) arousals·h-1; p=0.258). Overall adherence was not different except in those with poor early adherence (<4 h·day-1) who increased their use after polysomnographic titration (mean difference: PSG 95 (95% CI 29-161) min·day-1 versus control -23 (95% CI -86-39) min·day-1; p=0.01). Arterial carbon dioxide tension, somnolence and sleep quality improved in both groups. There were no differences in nocturnal gas exchange or overall measures of HRQoL.NIV titrated with PSG is associated with less PVA but not less sleep disruption when compared with therapy titrated during daytime alone.

A prospective cohort study of thoracic ultrasound in acute respiratory failure: the C3PO protocol.

OBJECTIVES: This study was performed to assess the clinical utility of a standardised thoracic ultrasound examination when added to standard care in patients with acute respiratory failure admitted to an intermediate care unit. This study aimed to assess the impact on clinical diagnosis, clinician confidence and management. Ultrasound has been shown to have utility in patients admitted to intensive care and emergency; however, utility in a ward setting is unknown. DESIGN: Prospective cohort study. SETTING: Tertiary hospital in Melbourne, Australia. PARTICIPANTS: 50 patients with acute respiratory failure requiring admission to an intermediate care unit. MAIN OUTCOME MEASURES: (1) Change in clinical diagnosis or additional clinical diagnosis following thoracic ultrasound. (2) Change in diagnostic confidence following thoracic ultrasound. (3) Change to management following thoracic ultrasound. RESULTS: In 34% of patients, ultrasound detected unexpected findings that changed or added to the clinical diagnosis. Diagnostic confidence was increased in 44%, and the treating clinician altered the management plan in 30% as a result of the ultrasound. Ultrasound was particularly useful in clarifying the diagnosis in patients with multiple initial diagnoses, reducing to a single diagnosis in 69%. CONCLUSIONS: Thoracic ultrasound has clinical utility in non-intubated adults with acute respiratory failure managed outside intensive care settings. It changed aetiological diagnosis, increases diagnostic confidence and altered clinical management in one out of three patients scanned. Our results suggest extended utility of thoracic ultrasound in acute respiratory failure to a broader context outside the intensive care unit population.

Framing of mobility items: a source of poor agreement between preference-based health-related quality of life instruments in a population of individuals receiving assisted ventilation.

PURPOSE: To explore the influence of descriptive differences in items evaluating mobility on index scores generated from two generic preference-based health-related quality of life (HRQoL) instruments. METHODS: The study examined cross-sectional data from a postal survey of individuals receiving assisted ventilation in two state/province-wide home mechanical ventilation services, one in British Columbia, Canada and the other in Victoria, Australia. The Assessment of Quality of Life 8-dimension (AQoL-8D) and the EQ-5D-5L were included in the data collection. Graphical illustrations, descriptive statistics, and measures of agreement [intraclass correlation coefficients (ICCs) and Bland-Altman plots] were examined using index scores derived from both instruments. Analyses were performed on the full sample as well as subgroups defined according to respondents' self-reported ability to walk. RESULTS: Of 868 individuals receiving assisted ventilation, 481 (55.4%) completed the questionnaire. Mean index scores were 0.581 (AQoL-8D) and 0.566 (EQ-5D-5L) with 'moderate' agreement demonstrated between the two instruments (ICC = 0.642). One hundred fifty-nine (33.1%) reported level 5 ('I am unable to walk about') on the EQ-5D-5L Mobility item. The walking status of respondents had a marked influence on the comparability of index scores, with a larger mean difference (0.206) and 'slight' agreement (ICC = 0.386) observed when the non-ambulant subgroup was evaluated separately. CONCLUSIONS: This study provides further evidence that between-measure discrepancies between preference-based HRQoL instruments are related in part to the framing of mobility-related items. Longitudinal studies are necessary to determine the responsiveness of preference-based HRQoL instruments in cohorts that include non-ambulant individuals.

Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness.

The aim of the present study was to determine whether lung volume recruitment (LVR) acutely increases respiratory system compliance (Crs) in individuals with severe respiratory muscle weakness (RMW). Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12) and healthy controls (n=12) underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O-1, p<0.001). Immediately after LVR, Crs increased by 39.5±9.8% to 50±7 mL·cmH2O-1 in individuals with RMW (p<0.05), while no significant change occurred in controls (p=0.23). At 1 h and 2 h post-treatment, there were no within-group differences in Crs compared to baseline (all p>0.05). LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05). During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05). LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique.

Physician-performed chest ultrasound: progress and future directions.

BACKGROUND: Pleural ultrasound guidance reduces complications of pleural procedures, and lung ultrasound can diagnose the cause of acute respiratory failure. Yet as recently as 5 years ago, many respiratory physicians lacked sufficient access, training and expertise to perform a chest ultrasound. AIMS: This study examines whether progress has been achieved in chest ultrasound amongst respiratory physicians in Australia and New Zealand. METHODS: We conducted a web-based chest ultrasound survey of adult respiratory physicians across Australia and New Zealand. We also surveyed advanced trainees. RESULTS: The response rate was 38% among respiratory physicians. Between 2011 and 2016, access to bedside ultrasound increased from 53 to 90%. The proportion arranging ultrasound guidance for pleural aspiration rose from 66 to 95%. The proportion demonstrably competent in pleural ultrasound increased from 4 to 21%. In 2016, 67% of physicians and 80% of advanced trainees reported available workplace supervision for ultrasound training. Use of lung ultrasound to diagnose acute pulmonary oedema and consolidation improved from 2011 but remained low at 25 and 20% respectively. CONCLUSION: These results establish pleural ultrasound guidance for pleural procedures as the standard of care in our region. However, lung ultrasound remains underutilised. Ultrasound training can and should be incorporated into specialist respiratory training.

Care Practices and Health-related Quality of Life for Individuals Receiving Assisted Ventilation. A Cross-National Study.

RATIONALE: Comparisons of home mechanical ventilation services have demonstrated considerable regional variation in patient populations managed with this therapy. The respiratory care practices used to support individuals receiving assisted ventilation also appear to vary, but they are not well described. It is uncertain whether differences in the approach to care could influence health outcomes for individuals receiving assisted ventilation. OBJECTIVES: We sought to identify and describe the respiratory care practices of home ventilation providers in two different regions and determine whether care practice differences influence health-related quality of life. METHODS: We conducted a cross-national survey of individuals receiving assisted ventilation managed by two statewide home mechanical ventilation providers, one in Victoria, Australia, and the other in British Columbia, Canada. The survey was used to evaluate care practices, functional and physical measures, socioeconomic attributes, and health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Overall, 495 individuals receiving assisted ventilation (57.2%) responded to the survey. Responders had clinical attributes similar to those of nonresponders. The Canadian population had a greater proportion of individuals with neuromuscular disorders and lesser percentages with obesity hypoventilation syndrome and chronic obstructive pulmonary disease. We also found marked differences in the reported care practices in Canada that were not fully explained by population differences. Subjects in the Canadian sample were more likely than their Australian counterparts to use invasive mechanical ventilation (24.2% vs. 2.5%; P < 0.001), to use routine airway clearance techniques (28.9% vs. 14.8%; P < 0.001), and to have had home implementation of noninvasive ventilation (39.9% vs. 3.6%; P < 0.001). Subjects in the Australian population were more likely than those in Canada to have undergone polysomnography to evaluate their ventilatory support (93.9% vs. 37.4%; P < 0.001). There was no difference in summary measures of health-related quality of life between the two sites. In a multivariable regression model, age, ability to perform activities of daily living, physical function, employment, and household income were all independently associated with health-related quality of life, but neither geographic location (Canada vs. Australia) nor underlying diagnosis were significant factors in the model. CONCLUSIONS: In two cohorts of individuals receiving assisted ventilation, one in Australia and the other in Canada, we found marked differences in both the care practices employed and the populations served. Despite these regional differences, measures of health-related quality of life were not different. Further research is required to examine costly or burdensome interventions that are currently used routinely in the management of individuals receiving assisted ventilation.

Systematic review of non-invasive positive pressure ventilation for chronic respiratory failure.

BACKGROUND: This systematic review examined the effect of non-invasive positive pressure ventilation (NIPPV) on patient reported outcomes (PROs) and survival for individuals with or at risk of chronic respiratory failure (CRF). METHODS: Randomised controlled trials (RCTs) and prospective non-randomised studies in those treated with NIPPV for CRF were identified from electronic databases, reference lists and grey literature. Diagnostic groups included in the review were amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), Duchenne muscular dystrophy (DMD), restrictive thoracic disease (RTD) and obesity hypoventilation syndrome (OHS). RESULTS: Eighteen studies were included and overall study quality was weak. Those with ALS/MND had improved somnolence and fatigue as well as prolonged survival with NIPPV. For OHS, improvements in somnolence and fatigue, dyspnoea and sleep quality were demonstrated, while for RTD, measures of dyspnoea, sleep quality, physical function and health, mental and emotional health and social function improved. There was insufficient evidence to form conclusions regarding the effect of NIPPV for those with DMD. CONCLUSIONS: This review has demonstrated that NIPPV influences PROs differently depending on the underlying cause of CRF. These findings may provide assistance to patients and clinicians to determine the relative costs and benefits of NIPPV therapy and also highlight areas in need of further research.

Inpatient and long-term outcomes of individuals admitted for weaning from mechanical ventilation at a specialized ventilation weaning unit.

BACKGROUND: Weaning from invasive mechanical ventilation (IMV) in specialized weaning units has been demonstrated to be safe and cost-effective. Success rates and outcomes vary widely, probably relating to patient factors and unit expertise. METHODS: An audit was undertaken of patients admitted for weaning from IMV at the Austin Hospital Ventilation Weaning Unit (VWU) between March 2002 and January 2008. Weaning success, complications and both in-hospital and long-term mortality were examined and regression analysis was undertaken to examine factors related to these outcomes. RESULTS: Seventy-eight patients were admitted to the VWU after a median of 27 days of IMV at their referring centre. Weaning success rate (ventilator free or nocturnal non-invasive ventilation only) was 78.2% (n = 61). Inpatient mortality was 10.2% (n = 8) and serious complications were infrequent. Progressive neuromuscular disease (odds ratio 0.10) and sepsis during admission to the VWU (odds ratio 0.09) were predictive of weaning failure at discharge. Overall survival at 12 months following discharge from the VWU was 66.7% (n = 52) with most survivors residing in the community. Increasing age (hazard ratio 1.93), referral from rural or outer metropolitan centres (hazard ratio 3.57 and 2.37 respectively) and a diagnosis of chronic obstructive pulmonary disease were associated with increased long-term mortality. CONCLUSION: High rates of weaning success with infrequent complications and low mortality were achieved in this specialized non-intensive care unit-based weaning unit. The VWU may provide a useful template for the development of similar units elsewhere.

Low utilisation of diagnostic microbiology for community acquired pneumonia in regional Victoria.

AIMS: Diagnostic microbiology for community acquired pneumonia (CAP) provides useful information for patient management, infection control and epidemiological surveillance. Newer techniques enhance that information and the time interval for obtaining results. An audit of diagnostic microbiology utilisation, microbiological aetiology, and influence of results on prescribing practices in CAP in a regional Australian hospital setting was performed. METHODS: Clinical, microbiological and outcome data were collected by medical record review of patients discharged from Ballarat Hospital with a diagnosis of CAP over a 12 month period. RESULTS: Of 184 identified CAP episodes, 47 (25.5%) had no diagnostic microbiology performed. Respiratory virus polymerase chain reaction (PCR) was rarely performed (2.7% of all episodes). Acute serology was frequently requested, however paired acute and convalescent serology was infrequently performed (5/75 testing episodes; 6.7%). CAP severity was not correlated with microbiological investigation intensity. The most common pathogens identified were Streptococcus pneumoniae and Mycoplasma pneumoniae (5.4% and 2.2%, respectively). Diagnostic testing appeared to rarely influence antimicrobial prescribing. CONCLUSIONS: In this setting, diagnostic microbiological tests such as respiratory virus PCR and urinary antigen tests are under-utilised. In contrast, sputum and serological investigations are commonly requested, however rarely influence practice. Interventions to facilitate efficient usage of diagnostic microbiology are required.

Interstitial lung disease in a patient treated with oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) for metastatic colorectal cancer.

BACKGROUND: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (FOLFOX) is a common chemotherapeutic regimen for advanced colorectal cancer. Here, we present a case of interstitial lung disease associated with FOLFOX therapy. CASE REPORT: A 74-year-old man with a history of metastatic colorectal cancer was admitted with a four week history of progressive dyspnoea and evidence of severe respiratory failure. He had recently completed six cycles of FOLFOX chemotherapy in the months prior to presentation. Investigations did not reveal convincing evidence of infection or pulmonary embolism. CT chest demonstrated widespread pulmonary infiltrates and interlobular septal thickening. The patient was commenced on both broad spectrum antibiotic therapy and high dose corticosteroid treatment however his respiratory failure continued to progress. The patient died four days after admission due to progressive respiratory failure. Subsequent post-mortem examination demonstrated evidence of diffuse alveolar damage without evidence of tumour infiltration, infection or pulmonary embolism. CONCLUSIONS: Although infrequent, pulmonary toxicity can occur in association with FOLFOX therapy. Cessation of therapy and prompt initiation of corticosteroids may improve outcomes.