Paraquat ingestion in an adult with cystic fibrosis (CF): Diagnostic and management dilemmas.

N,N'-dimethyl-4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long-term sequelae of paraquat, namely osteonecrosis. Our case is the first to describe osteonecrosis of the knee in the context of paraquat toxicity. Survival following ingestion remains poor with a high associated mortality. However, timely treatment with NAC and immunosuppression may impact on survival. In those patients who do survive the acute phase post ingestion, follow-up over years may be required to detect the long-term effects of paraquat on bone health.

The Effectiveness of Ultraviolet-C (UV-C) Irradiation on the Viability of Airborne Pseudomonas aeruginosa.

Pseudomonas aeruginosa (Pa) is the predominant bacterial pathogen in people with cystic fibrosis (CF) and can be transmitted by airborne droplet nuclei. Little is known about the ability of ultraviolet band C (UV-C) irradiation to inactivate Pa at doses and conditions relevant to implementation in indoor clinical settings. We assessed the effectiveness of UV-C (265 nm) at up to seven doses on the decay of nebulized Pa aerosols (clonal Pa strain) under a range of experimental conditions. Experiments were done in a 400 L rotating sampling drum. A six-stage Andersen cascade impactor was used to collect aerosols inside the drum and the particle size distribution was characterized by an optical particle counter. UV-C effectiveness was characterized relative to control tests (no UV-C) of the natural decay of Pa. We performed 112 tests in total across all experimental conditions. The addition of UV-C significantly increased the inactivation of Pa compared with natural decay alone at all but one of the UV-C doses assessed. UV-C doses from 246-1968 µW s/cm2 had an estimated effectiveness of approximately 50-90% for airborne Pa. The effectiveness of doses ≥984 µW s/cm2 were not significantly different from each other (p-values: 0.365 to ~1), consistent with a flattening of effectiveness at higher doses. Modelling showed that delivering the highest dose associated with significant improvement in effectiveness (984 µW s/cm2) to the upper air of three clinical rooms would lead to lower room doses from 37-49% of the 8 h occupational limit. Our results suggest that UV-C can expedite the inactivation of nebulized airborne Pa under controlled conditions, at levels that can be delivered safely in occupied settings. These findings need corroboration, but UV-C may have potential applications in locations where people with CF congregate, coupled with other indoor and administrative infection control measures.

Screening for obstructive sleep apnoea in patients with serious mental illness.

OBJECTIVE: Patients with serious mental illness (SMI) are at increased risk of obstructive sleep apnoea (OSA). Despite this, OSA is frequently under-recognised in the psychiatric population. This study describes the results of OSA screening in SMI patients. METHOD: Patients with SMI attending a metropolitan mental health clinic were screened for OSA using the OSA50, STOP-BANG Questionnaire (SBQ), Epworth Sleep Score (ESS) and the Pittsburgh Sleep Quality Index (PSQI). They were then offered diagnostic sleep testing via ResMed ApneaLinkTM and polysomnography. RESULTS: Of the 65 patients recruited, 65% had a primary diagnosis of schizophrenia or schizoaffective disorder, 85% were on antipsychotic medications and the majority were obese. Approximately 50% of patients reported poor sleep quality via the PSQI, in contrast to 12% with elevated daytime sleepiness via the ESS. 46% of our cohort were at risk of OSA due to an elevated OSA50 or SBQ. Of the five patients who agreed to proceed to diagnostic sleep testing, three were diagnosed with OSA. CONCLUSION: A high proportion of patients with psychiatric illness are at risk of sleep-disordered breathing. Sleep dissatisfaction is high. The low uptake of sleep investigation requires improved patient engagement to improve OSA diagnosis in this high-risk group.

Cohort study of sleep quality in adult patients with acute pulmonary exacerbations of cystic fibrosis.

BACKGROUND: The impact of an acute pulmonary exacerbation of cystic fibrosis (CF) on sleep quality has not been established. Patients have greater burden of symptoms, higher intensity of therapy and are often admitted to hospital outside of their usual sleeping environment. AIMS: To evaluate the prevalence of, and factors associated with, poor sleep quality in adult patients admitted to hospital with an acute exacerbation of CF lung disease. METHODS: This prospective, observational study determined the prevalence of impaired sleep quality and associated factors in adult patients admitted to a single CF unit with an acute pulmonary exacerbation of CF. Sleep quality was defined by the Pittsburgh Sleep Quality Index (PSQI), with >5 indicating poor sleep quality. Data were obtained through patient questionnaires, chart review and examination. RESULTS: Sixty-six percent of patients had impaired sleep quality. Patients with poor sleep had more sleep disruption due to pain (median response 'mild sleep disruption' vs 'no sleep disruption'; P = 0.003) and insomnia (mean Insomnia Severity Index (ISI) 13 vs 5; P < 0.001). In patients with symptoms of restless legs, poor sleepers had worse symptoms (mean International Restless Legs Severity Score (IRLSS) 15 vs 5; P = 0.029). Univariate modelling showed relationships between PSQI and symptoms of depression and anxiety as well as with sleep disruption due to pain, general noise and nursing observations. In a multivariable model, ISI was the only variable that remained significantly associated with PSQI. Mean PSQI score increased 0.58 units for each 1 unit increase in ISI (95% CI 0.42-0.73; P < 0.001). CONCLUSIONS: Poor sleep quality is common among patients admitted with an acute exacerbation of CF and is strongly associated with insomnia symptoms in this cohort.

Safety and efficacy of high-flow nasal cannula therapy in acute hypercapnic respiratory failure: a retrospective audit.

BACKGROUND: While the role of high-flow nasal cannulae (HFNC) in the management of respiratory failure continues to expand, few studies describe its use in acute hypercapnic respiratory failure. AIMS: In this retrospective study, we assessed the safety and efficacy of HFNC for the treatment of acute hypercapnic respiratory failure. METHODS: Admissions with acute hypercapnic respiratory failure to a thoracic medicine unit at a tertiary centre between January and August 2018 were included if treated with either HFNC or non-invasive ventilation (NIV). The primary outcome was post-treatment change in arterial pCO2 . Demographics, comorbidities, length of stay, readmission rate and mortality were also collected. RESULTS: Sixty-four patients were identified, comprising 69 presentations grouped according to initial treatment: HFNC (n = 24) or NIV (n = 45). Patients in the NIV group had more severe blood gas derangement. In both groups, mean arterial pCO2 improved significantly (-10 (95% confidence interval: -14 to -6) mmHg) from baseline with no evidence of a differential effect between groups. Six (25%) patients, of whom three had comorbid obesity and two had sleep-disordered breathing, were transitioned from HFNC to NIV. No significant differences in hospital length of stay, 30-day readmission rate or 90-day mortality were observed. CONCLUSIONS: HFNC might be a reasonable initial treatment for patients with mild acute hypercapnic respiratory failure who do not have comorbid obesity or sleep-disordered breathing. A prospective study might help identify clinical factors or phenotypes predictive of success with this treatment modality.

Outcomes of artery embolisation for cystic fibrosis patients with haemoptysis: a 20-year experience at a major Australian tertiary centre.

There are no published data on Australian adult cystic fibrosis (CF) patient outcomes post bronchial arterial embolisation (BAE). We report 20 years of experience of BAE at a major Australian tertiary adult CF centre, where 46 patients underwent 100 BAE during this period. Mortality rate was comparable to previous studies (4% per year) and most who died had repeat BAE requirements. A higher proportion (9 out of 45) of patients were transplanted compared to previous publications. Repeat BAE was common and significantly higher in patients already on tranexamic acid.

Evaluation of inpatient oxygen therapy in hypercapnic chronic obstructive pulmonary disease.

BACKGROUND: High concentration oxygen therapy in hypercapnic chronic obstructive pulmonary disease (COPD) is associated with increased mortality. In ward-based patients with acute exacerbation of COPD and hypercapnia, this study examines oxygen prescription and the association between high concentration oxygen therapy and adverse outcome. AIMS: To investigate the association between over-oxygenation and in-hospital adverse events. METHODS: Inpatients with acute exacerbation of hypercapnic COPD at a tertiary Australian hospital over a 1-year period were retrospectively identified. Oxygen prescription and therapy was determined based on chart review. Over-oxygenation was defined as ≥10% of nursing chart observations recording oxygen delivery with oxygen saturation above 92%. A composite adverse outcome was defined as medical emergency team response, recommencement of non-invasive ventilation or death. The association between over-oxygenation and adverse outcome was assessed using survival analysis and conditional logistic regression modelling. RESULTS: The study cohort comprised 106 unique patients and 157 admissions. Oxygen prescription was recorded in 132 (84%) and over-oxygenation occurred in 97 (62%) admissions. Over-oxygenation was higher in non-respiratory ward admissions (76% vs 57%, P = 0.03) and those without any form of oxygen prescription (84% vs 58%, P = 0.01). During follow up, 23 (22%) patients experienced an adverse event. Cox proportional hazards modelling found weak evidence for increased risk of an adverse event in over-oxygenated patients (hazard ratio 2.5; 95% confidence interval 0.8-7.3, P = 0.10). Conditional logistic regression, after matching on age, Charlson comorbidity category and length of follow up, found a similar estimate of association (hazard ratio 2.6; 95% confidence interval 0.8-8.7, P = 0.12). CONCLUSIONS: Over-oxygenation to hypercapnic COPD inpatients is common and rates of oxygen prescription are suboptimal. We found weak evidence of association between over-oxygenation and adverse events, likely due to low statistical power. Larger prospective studies are needed.

Multiple Sleep Latency Test: when are 4 naps enough?

STUDY OBJECTIVES: The Multiple Sleep Latency Test (MSLT) is central to the diagnosis of narcolepsy and idiopathic hypersomnia. This study is the first to assess the impact of a 5-nap protocol on meeting MSLT-derived diagnostic criteria in a general cohort referred for MSLT, without selection bias. METHODS: Data for all MSLTs performed at 2 tertiary sleep units in Australia between May 2012 and May 2018 were retrospectively assessed for the impact of the fifth nap on mean sleep latency (MSL) and sleep onset rapid eye movement periods. RESULTS: There were 122 MSLTs included. The MSL was 8.7 ± 5.1 minutes after 4 naps, compared with 9.2 ± 5.2 minutes for 5 naps (P < .0001). In 8 cases, inclusion of the fifth nap changed the MSL to a value above the diagnostic threshold of 8 minutes. There were no instances in which the MSL moved to ≤ 8 minutes based on fifth nap data. A sleep onset rapid eye movement period occurred in the fifth nap in 9 patients and altered the interpretation in 2 cases. CONCLUSIONS: The fifth nap in an MSLT is associated with an increased MSL, although this difference is rarely clinically significant. In patients with borderline MSL or 1 sleep onset rapid eye movement period after 4 naps, a fifth nap can alter the outcome and should be performed. However, for many cases, a 4-nap MSLT protocol will suffice, potentially allowing resource savings without compromising diagnostic accuracy. We propose the adoption of a conditional 4-nap or 5-nap protocol based on specific criteria.

Use of a limited-channel device for obstructive sleep apnoea diagnosis in a tertiary sleep disorders centre.

BACKGROUND: A major impediment to the provision of obstructive sleep apnoea (OSA) treatment is reliance on labour-intensive and costly laboratory-based polysomnography (PSG). AIMS: To investigate if measurement of oximetry and nasal flow through the ApneaLink device (AL) could identify patients with moderate-severe OSA among those referred for PSG to a tertiary sleep service. METHODS: New referrals to The Prince Charles Hospital Sleep Disorders Centre were assessed for suitability. Demographics, anthropometrics, Epworth Sleepiness and OSA50 scores were collected. Exclusion criteria included age <18 years, pregnancy, significant cognitive impairment, poorly controlled psychiatric disorder, domiciliary oxygen and prior OSA treatment. Participants underwent concurrent type 1 PSG and AL assessments. RESULTS: One hundred participants had a mean age of 55 years (standard deviation 17) and were 49% male. Forty-eight (48%) had moderate-severe OSA on PSG. Composite variable AL 3% oxygen desaturation index ≥16 and AL apnoea-hypopnoea index (AHI) ≥15 had receiver operator characteristic area under the curve of 0.87, sensitivity of 80% and specificity of 94% for PSG AHI ≥15. The three false-positives seen with this composite variable had PSG AHI 11-14 and Epworth Sleepiness Score 6-17. The various composites of AL, anthropometric and questionnaire variables did not improve the AUC or specificity but did improve sensitivity. CONCLUSIONS: AL is useful in the diagnosis of moderate-severe OSA in patients referred to a tertiary sleep disorders centre. This could lessen reliance on PSG, expedite OSA care, lead to significant cost savings and make diagnosis of OSA more available in non-urban areas.

Improving service delivery for neuromuscular diseases: a survey of consumers at a tertiary Australian hospital.

Patients with neuromuscular diseases benefit from coordinated multidisciplinary care to achieve best outcomes. The integration of multi-specialty healthcare delivered in a single clinic can be challenging for service providers due to cost and resource limitation. Our cross-sectional survey of 53 adult patients with neuromuscular disease across Queensland revealed only 27% support the introduction of an integrated multidisciplinary clinic. The most cited reason for opposition to a multidisciplinary clinic was a perceived loss of contact with one's usual doctor. Modifying service delivery in neuromuscular disease is a complex undertaking and will need input from numerous stakeholders.

Mortality in acute non-invasive ventilation.

A prospective study of non-invasive ventilation at The Prince Charles Hospital outside of the intensive care unit from March 2015 to March 2016 was performed. Overall 69 patients were included. Acute hypercapnic respiratory failure was the most common indication (n = 59; 85%). 49 (71%) had multifactorial respiratory failure. 15 (22%) patients died. Premorbid inability to perform self-care (P = 0.001) and the combination of mean pH < 7.25 and mean PaCO2 ≥ 75 mmHg within 2 h of NIV initiation (P = 0.037) were significantly associated with mortality. There was a non-significant association between older age and mortality.

Adult-onset Pompe's disease presenting with insidious hypercapnic respiratory failure.

Orthopnoea is commonly attributed to heart failure but can be caused by diaphragm weakness, which, when severe, is often associated with hypercapnic respiratory failure. Bilateral diaphragm weakness is generally due to systemic nerve or muscle disease and usually occurs in the setting of severe generalized muscle weakness, but the diaphragm can be the initial or only muscle involved. Here, we report the case of a 39-year-old female who presented with slowly progressive orthopnoea and daytime somnolence. Pulmonary function studies and polysomnogram confirmed bilateral diaphragm weakness complicated by nocturnal hypoventilation and she was subsequently diagnosed with adult-onset Pompe's disease, a rare metabolic myopathy.

Inhaled antibiotics in Cystic Fibrosis (CF) and non-CF bronchiectasis.

Bronchiectasis is a pathological diagnosis describing dilatation of the airways and is characterized by chronic lung sepsis. Bronchiectasis has multiple etiologies, but is usually considered in terms of whether it is due to the genetic disorder cystic fibrosis (CF) or secondary to other causes (non-CF bronchiectasis, NCFB). Inhaled antibiotics are used in bronchiectasis to suppress bacterial pathogens and reduce long-term lung function decline. The majority of the literature on inhaled antibiotics comes from studies on CF where the dominant bacterial pathogen in the airway is usually Pseudomonas aeruginosa. Thus, most aerosolized antibiotic regimens target this bacterium, but the emergence of molecular diagnostic methods has questioned this approach and more tailored strategies may need to be considered in CF based on the community composition of the lung microbiome. Similarly, the lung microbiome in NCFB has been found to be a complex polymicrobial one and the current practice of employing the same inhaled antibiotic regimes as are used in CF may no longer be appropriate in many patients. In this article, the use of inhaled antibiotics in CF and NCFB is considered in the light of improved understanding of the lung microbiome and why more tailored therapy may be needed based on molecular identification of the microbial pathogens present. The evidence for the use of currently available inhaled antibiotics and advances in inhaled drug packaging and delivery devices are discussed. Finally, the urgent need for prospective randomized clinical trials in CF and NCFB is highlighted and areas for future research identified.

Pregnancy and cystic fibrosis: Approach to contemporary management.

Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis.