Silver Nitrate-coated versus Standard Indwelling Pleural Catheter for Malignant Effusions: The SWIFT Randomized Trial.

Rationale: Tunneled, indwelling pleural catheters (IPCs) have been demonstrated to be an effective method of managing malignant pleural effusions. However, they allow pleurodesis and can therefore be removed in only a subset of patients. A novel, silver nitrate-coated IPC was developed with the intention of creating a rapid, effective chemical pleurodesis to allow more frequent and earlier catheter removal. This study represents the pivotal clinical trial evaluating that catheter versus the standard IPC. Objectives: To compare the efficacy of a novel silver nitrate-eluting indwelling pleural catheter (SNCIPC) with that of a standard, uncoated catheter. Methods: The SWIFT [A Pivotal Multi-Center, Randomized, Controlled, Single-Blinded Study Comparing the Silver Nitrate-Coated Indwelling Pleural Catheter (SNCIPC) to the Uncoated PleurX® Pleural Catheter for the Management of Symptomatic, Recurrent, Malignant Pleural Effusions] trial was a multicenter, parallel-group, randomized, controlled, patient-blind trial. Central randomization occurred according to a computer-generated schedule, stratified by site. Recruitment was from 17 secondary or tertiary care hospitals in the United States and 3 in the United Kingdom and included adult patients with malignant pleural effusion needing drainage, without evidence of lung entrapment or significant loculation. The intervention group underwent insertion of an SNCIPC with maximal fluid drainage, followed by a tapering drainage schedule. The control group received a standard, uncoated catheter. Follow-up was conducted until 90 days. The primary outcome measure was pleurodesis efficacy, measured by fluid drainage, at 30 days. Results: A total of 119 patients were randomized. Five withdrew before receiving treatment, leaving 114 (77 SNCIPC, 37 standard IPC) for analysis. The mean age was 66 years (standard deviation, 11). More patients in the SNCIPC group were inpatients (39% vs. 14%; P = 0.009). For the primary outcome, pleurodesis rates were 12 (32%) of 37 in the control group and 17 (22%) of 77 in the SNCIPC group (rate difference, -0.10; 95% confidence interval, -0.30 to 0.09). Median time to pleurodesis was 11 days (interquartile range, 9 to 23) in the control group and 4 days (interquartile range, 2 to 15) in the SNCIPC group. No significant difference in treatment-related adverse event rates was noted between groups. Conclusions: The SNCIPC did not improve pleurodesis efficacy compared with a standard IPC. This study does not support the wider use of the SNCIPC device. Clinical trial registered with www.clinicaltrials.gov (NCT02649894).

Thoracic ultrasound competence for ultrasound guided pleural procedures: The creation and validation of an assessment tool for use in the certification of basic thoracic ultrasound competence.

OBJECTIVES: Focused thoracic ultrasound (TUS) provides an increased safety profile when undertaking invasive pleural procedures. This has led to the requirement for defined curricula, high quality teaching and robust, validated assessment tools among physicians to ensure patient safety and clinical excellence. Current UK practice is based almost exclusively on expert consensus, but assessment methods employed have been shown to have low reliability and validity and are potentially open to bias. As a result, several assessment tools have been developed, although each has its own limitations. METHODS: This study aimed to develop and validate an assessment tool corresponding to those skills associated with the most basic level of practice, defined recently as an emergency level operator in the British Thoracic Society Training Standards for Thoracic Ultrasound. RESULTS: A total of 27 candidates were enrolled by two examiners based in Belfast and Oxford over a 10-month period between February and November 2019. Mean score of the inexperienced group was 44.3 (95% CI 39.2-49.4, range 28-54) compared with 74.9 (95% CI 72.8-77, range 64-80) in the experienced group providing an estimated mean difference of 30.7 between the two groups (95% CI 24.7-36.7; p < .001). CONCLUSIONS: This tool appears to discriminate between trainees with limited experience of TUS performance and those with no experience. It has the potential to form part of the assessment strategy for trainees in the United Kingdom and beyond, alongside well established assessment tools in postgraduate training.

Ambulatory management of secondary spontaneous pneumothorax: a randomised controlled trial.

Secondary spontaneous pneumothorax (SSP) is traditionally managed with an intercostal chest tube attached to an underwater seal. We investigated whether use of a one-way flutter valve shortened patients' length of stay (LoS).This open-label randomised controlled trial enrolled patients presenting with SSP and randomised to either a chest tube and underwater seal (standard care: SC) or ambulatory care (AC) with a flutter valve. The type of flutter valve used depended on whether at randomisation the patient already had a chest tube in place: in those without a chest tube a pleural vent (PV) was used; in those with a chest tube in situ, an Atrium Pneumostat (AP) valve was attached. The primary end-point was LoS.Between March 2017 and March 2020, 41 patients underwent randomisation: 20 to SC and 21 to AC (13=PV, 8=AP). There was no difference in LoS in the first 30 days following treatment intervention: AC (median=6 days, IQR 14.5) and SC (median=6 days, IQR 13.3). In patients treated with PV there was a high rate of early treatment failure (6/13; 46%), compared to patients receiving SC (3/20; 15%) (p=0.11) Patients treated with AP had no (0/8 0%) early treatment failures and a median LoS of 1.5 days (IQR 23.8).There was no difference in LoS between ambulatory and standard care. Pleural Vents had high rates of treatment failure and should not be used in SSP. Atrium Pneumostats are a safer alternative, with a trend towards lower LoS.

UK consensus statement on the diagnosis of inducible laryngeal obstruction in light of the COVID-19 pandemic.

Prior to the COVID-19 pandemic, laryngoscopy was the mandatory gold standard for the accurate assessment and diagnosis of inducible laryngeal obstruction. However, upper airway endoscopy is considered an aerosol-generating procedure in professional guidelines, meaning routine procedures are highly challenging and the availability of laryngoscopy is reduced. In response, we have convened a multidisciplinary panel with broad experience in managing this disease and agreed a recommended strategy for presumptive diagnosis in patients who cannot have laryngoscopy performed due to pandemic restrictions. To maintain clinical standards whilst ensuring patient safety, we discuss the importance of triage, information gathering, symptom assessment and early review of response to treatment. The consensus recommendations will also be potentially relevant to other future situations where access to laryngoscopy is restricted, although we emphasize that this investigation remains the gold standard.

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Manometry performed at indwelling pleural catheter insertion to predict unexpandable lung.

BACKGROUND: The finding of unexpandable lung (UL) at an early timepoint is of increasing importance in guiding treatment decisions in patients with malignant pleural effusion (MPE). Pleural manometry is the most common technique to delineate UL, however it has never been measured via an indwelling pleural catheter (IPC). To further the evidence base we analysed all patients in the IPC-PLUS study who had manometry performed during IPC insertion for the ability to predict substantial UL using manometry. METHODS: All patients enrolled in IPC-PLUS who had manometry performed at IPC insertion and radiographic assessment of UL at day 10 were included. Elastance curves were visually inspected for each patient. Initial pleural pressure, closing pleural pressure, and terminal elastance were analysed for their differences and predictive ability in those with substantial UL, defined as ≥25% entrapment on chest radiography. RESULTS: A total of 89 patients had manometry performed at IPC insertion with subsequent radiographic assessment of UL and interpretable elastance curves. Those with substantial UL had a significantly lower median closing pleural pressure (-15.00 vs. 0.00 cmH2O, P=0.012) and higher terminal elastance (12.03 vs. 8.59 cmH2O/L, P=0.021) compared to a combined group with no or partial UL. However, the predictive ability of these factors to discriminate substantial UL was poor, with areas under the receiver operating characteristic curves of 0.695 and 0.680 for closing pleural pressure and elastance respectively. CONCLUSIONS: Our results suggest that manometry is not useful in accurately predicting substantial UL when used via an IPC at the time of insertion.

British Thoracic Society Training Standards for Thoracic Ultrasound (TUS).

INTRODUCTION: The British Thoracic Society (BTS) responded to a call from the pleural community to establish this new Training Standard to detail the capabilities in practice for thoracic ultrasound (TUS), which will build on the previous curricula and extend the remit to include training for the emergency provision of TUS. METHODS: BTS convened a working group to produce a set of Training Standards. RESULTS: This document provides a comprehensive Training Standard for TUS facilitating timely and improved management of patients with respiratory presentations, particularly (but not exclusively) pleural pathologies. DISCUSSION: The Training Standards document will be widely disseminated.

Training opportunities in thoracic ultrasound for respiratory trainees: are current guidelines practical?

Introduction: Respiratory trainees in the UK face challenges in meeting current Royal College of Radiologists (RCR) Level 1 training requirements for thoracic ultrasound (TUS) competence, specified as attending 'at least one session per week over a period of no less than 3 months, with approximately five scans per session performed by the trainee (under supervision of an experienced practitioner)'. We aimed to clarify where TUS training opportunities currently exist for respiratory registrars. Methods: Data were collected (over a 4-week period) to clarify the number of scans (and therefore volume of training opportunities) within radiology departments and respiratory services in hospitals in the South West, North West deaneries and Oxford. Results: 14 hospitals (including three tertiary pleural centres) provided data. Of 964 scans, 793 (82.3%) were conducted by respiratory teams who performed a mean of 17.7 scans per week, versus 3.1 TUS/week in radiology departments. There was no radiology session in any hospital with ≥5 TUS performed, whereas 8/14 (86%) of respiratory departments conducted such sessions. Almost half (6/14) of radiology departments conducted no TUS scans in the period surveyed. Conclusions: The currently recommended exposure of regularly attending a list or session to undertake five TUS is not achievable in radiology departments. The greatest volume of training opportunities exists within respiratory departments in a variety of scheduled and unscheduled settings. Revision of the competency framework in TUS, and where this is delivered, is required.

Is it safe to SCUBA dive with asthma?

Introduction: Internationally it is estimated that six million people participate in self-contained underwater breathing apparatus (SCUBA) diving each year. Registries suggest a significant proportion of divers have a current or historical diagnosis of asthma. Previously individuals with asthma were prohibited from diving, however, several contemporary guidelines suggest a select population of patients with asthma may be able to dive with an acceptable degree of risk. Areas covered: Divers with asthma may be at an increased risk of a variety of diving-related medical injuries including; pulmonary barotrauma (PBT), pneumothorax, pneumomediastinum, arterial gas embolism (AGE), reduction in pulmonary function, bronchospasm and decompression sickness (DCS). This article will discuss the latest evidence on the incidence of adverse events in diving with a focus on those caused by asthma. Expert opinion: Physicians can be faced with the difficult task of counseling patients with asthma who wish to dive. This review article will aim to explore the current guidelines which can assist a physician in providing a comprehensive dive safety assessment.

Life threatening polyserositis post oesophagectomy.

A 46 year old lady presented three weeks after an oesophagectomy for oesophageal carcinoma with increasing breathlessness and a large left-sided pleural effusion. Computed tomography (CT) scan of her thorax, abdomen and pelvis revealed a large left-sided and small right-sided pleural effusions, a pericardial effusion, ascites and intra-abdominal lymphadenopathy. The patient underwent both pericardial and pleural fluid drainage, however, unfortunately, deteriorated despite these interventions with increasing oxygen requirements requiring nasal high flow oxygen on the Intensive Care Unit. Her pleural and pericardial collections resolved with colchicine and later introduction of prednisolone over a period of 5 weeks. Polyserositis is well recognised after cardiac surgery, but such a dramatic complication after thoracotomy for non-cardiac surgery has as not previously been reported. The polyserositis may relate to the induction chemotherapy combined with surgery.

Providing safe and effective pleural medicine services in the UK: an aspirational statement from UK pleural physicians.

Physicians face considerable challenges in ensuring safe and effective care for patients admitted to hospital with pleural disease. While subspecialty development has driven up standards of care, this has been tempered by the resulting loss of procedural experience in general medical teams tasked with managing acute pleural disease. This review aims to define a framework though which a minimum standard of care might be implemented. This review has been written by pleural clinicians from across the UK representing all types of secondary care hospital. Its content has been formed on the basis of literature review, national guidelines, National Health Service England policy and consensus opinion following a round table discussion. Recommendations have been provided in the broad themes of procedural training, out-of-hours management and pleural service specification. Procedural competences have been defined into descriptive categories: emergency, basic, intermediate and advanced. Provision of emergency level operators at all times in all trusts is the cornerstone of out-of-hours recommendations, alongside readily available escalation pathways. A proposal for minimum standards to ensure the safe delivery of pleural medicine have been described with the aim of driving local conversations and providing a framework for service development, review and risk assessment.

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion.

BACKGROUND: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS: Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS: The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS: Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).

Randomized Controlled Trial of Urokinase versus Placebo for Nondraining Malignant Pleural Effusion.

RATIONALE: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. METHODS: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. MEASUREMENTS AND MAIN RESULTS: Co-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). CONCLUSIONS: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).

Survival in Patients With Malignant Pleural Effusions Who Developed Pleural Infection: A Retrospective Case Review From Six UK Centers.

OBJECTIVE: Malignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014. METHODS: Survival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics. RESULTS: Of 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6). CONCLUSIONS: This small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression.

Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial.

CONTEXT: Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been determined. OBJECTIVE: To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea. DESIGN: Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year. INTERVENTION: Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis. MAIN OUTCOME MEASURE: Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables. RESULTS: Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range [IQR], 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a difference of −3.5 days (95% CI, −4.8 to −1.5 days; P < .001). There was no significant difference in quality of life. Twelve patients (22%) in the talc group required further pleural procedures compared with 3 (6%) in the IPC group (odds ratio [OR], 0.21; 95% CI, 0.04-0.86; P = .03). Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group (OR, 4.70; 95% CI, 1.75-12.60; P = .002). CONCLUSION: Among patients with malignant pleural effusion and no previous pleurodesis, there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN87514420.

Pseudochylothorax without pleural thickening: time to reconsider pathogenesis?

Pseudochylothorax (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion that is commonly associated with chronic inflammatory disorders such as tuberculosis or rheumatoid arthritis. Until now, there were only 15 published cases of arthritis-associated pseudochylothorax in the English language literature. Previous literature has suggested that pleural fluid cholesterol enrichment occurs in the context of grossly thickened (fibrotic) pleura over a prolonged period, usually > 5 years. We present six well-characterized cases of arthritis-associated pseudochylothorax, each notable due to their minimal pleural thickening. The median duration of symptoms (or arthritis, in the case of asymptomatic effusions) was 15 months. Such findings cast significant doubt on the conventional concepts of the pathogenesis of rheumatoid-associated pseudochylothorax. Clinicians should consider pseudochylothorax even in short-duration nonfibrotic pleural effusions.

An observational investigation of dysfunctional breathing and breathing control therapy in a problem asthma clinic.

OBJECTIVES: Dysfunctional breathing (DB) is recognized as an associated problem in patients with asthma and may be identified by the Nijmegen questionnaire. We conducted an observational study to determine if breathing control therapy (BCT) improved Nijmegen scores or asthma-related quality of life in patients attending a problem asthma clinic. METHODS: Nijmegen and Mini Asthma Quality of Life (Mini-AQLQ) questionnaires were completed. Patients with a positive Nijmegen (> or = 23, DB) were referred for BCT and progressive exercise testing (PET) to seek confirmation of dysfunctional breathing. Follow-up questionnaire data were collected at 6 months. RESULTS: A total of 102 patients were studied. The total mean Nijmegen score was 26.4 (range 1-61). Those with a score > or = 23 (DB group, n = 65, 64%) had significantly lower Mini-AQLQ (mean 2.83) than the non-DB group (n = 37, mean 4.12, 95% CI for difference 0.87, 1.87, p < 0.0001). There was a strong relationship between Nijmegen score and Mini-AQLQ (r = -0.63, p < 0.001) at baseline; 10 of 17 DB patients who completed PET showed inappropriate hyperventilation. Follow-up data, available for Nijmegen and Mini-AQLQ in 44 and 46 patients respectively, showed no significant change in either of these parameters. CONCLUSIONS: The strong relationship between Mini-AQLQ and Nijmegen scores and poor relationship between Nijmegen scores and PET-identified inappropriate hyperventilation suggest that a positive Nijmegen score overestimates the presence of dysfunctional breathing in patients with moderate to severe asthma. We found no evidence that a moderate intensity breathing control intervention had any impact on Nijmegen scores or asthma-related quality of life in this patient group.