Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

COVID-19: in the footsteps of Ernest Shackleton.

We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription-PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.

Transbronchial Cryobiopsy in Interstitial Lung Disease: Safety of a Standardized Procedure.

BACKGROUND: Transbronchial lung cryobiopsy (TBCB) plays an increasing role in the evaluation of diffuse parenchymal lung disease with acceptable diagnostic yield and safety profile compared with that of video-assisted thoracoscopic surgical lung biopsy on most reports. However, published outcomes with regard to safety and complication rates vary. We aim to determine the safety profile of TBCB when performed using a standardized protocol consistent with recently published expert guidelines. MATERIALS AND METHODS: We reviewed prospectively maintained databases from 5 Australian tertiary referral centers. The procedures were performed in accordance with a recent expert statement recommending standardization of TBCB procedures, in particular with fluoroscopy, a secured airway, and prophylactic bronchial blockers. Periprocedural complications were assessed along with clinical outcomes. RESULTS: A total of 121 patients underwent TBCB between August 2013 and August 2017 following a standardized protocol using general anesthesia. Of them, 84 patients (66.7%) were discharged on the day of the procedure. Pneumothorax occurred in 18 patients (14.9%), 13 (10.7%) of whom required chest tube drainage. Moderate bleeding occurred in 15 patients (13.2%) and severe bleeding in 1 (0.83%). Histopathologic diagnosis was made in 80 patients (66.1%). CONCLUSION: Pooled outcomes from Australian tertiary centers indicate that TBCB is safe when performed in a protocolized fashion. Active measures to anticipate and manage bleeding and to direct biopsy position result in low rates of major complications.

Changes in ventilation and perfusion following lower lobe endoscopic lung volume reduction (ELVR) with endobronchial valves in severe COPD.

BACKGROUND: We have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non-targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described. METHODS: Seven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6-minute walk tests (6MWT), St George's Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post-ELVR. RESULTS: Compared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L-0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m-274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33-42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%-37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%-35.60 ± 2.58%, p < 0.05) of the contralateral non-targeted upper zone. CONCLUSIONS: Within the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients.

Endoscopic Lung Volume Reduction in COPD: Improvements in Gas Transfer Capacity Are Associated With Improvements in Ventilation and Perfusion Matching.

BACKGROUND: Endoscopic lung volume reduction (ELVR) has been shown to improve lung function, quality of life, and exercise tolerance in patients with severe heterogeneous emphysema. Our study aims to determine the effect of ELVR on gas transfer capacity corrected for alveolar volume (KCO) and investigate the relationship between KCO and ventilation and perfusion (VQ) matching. We speculate on possible mechanisms for the observed changes METHODS:: Patients with severe chronic obstructive pulmonary disease were prospectively recruited and underwent unilateral upper lobe ELVR between 2012 and 2014. Each had respiratory function test and differential VQ scans at baseline, 1-, 3-, and 12-month post-ELVR. RESULTS: In total, 11 patients had 3 sets of respiratory function test (at baseline, 1, and 3 mo), whereas 7 had 4 sets (at baseline, 1, 3, and 12 mo). KCO improved by 10.3 (±7.5)% at 1 month (P=NS) and 39.8 (±15.4)% at 12 months (P<0.05). VQ of the nontargeted lung increased by 12.8 (±5.6)% and 7.9 (±2.3)%, respectively at 1 month, whereas those of the targeted lung both decreased (P<0.05). At 3 and 12 months, the VQ changes were similar to those at 1 month, though some were not statistically significant. CONCLUSIONS: ELVR results in improved KCO for at least 12 months. This may be explained by the VQ redistribution to the nontargeted and less emphysematous lung with improved VQ matching.

Impaired laryngopharyngeal sensitivity in patients with COPD: the association with swallow function.

Research indicates that patients with Chronic Obstructive Pulmonary Disease (COPD) have increased aspiration risk. Several factors may pre-dispose a patient to aspiration including a reduction in laryngopharyngeal sensitivity (LPS). Reduced LPS has been associated with increased aspiration risk in pathologies including stroke; however, this has not been examined in COPD. This study aims to explore possible associations between LPS and swallowing function in COPD patients, and determine whether a LPS predictive value may be used as a method of evaluating dysphagia risk in this patient population. Twenty participants with COPD underwent LPS discrimination testing, respiratory function testing, self-reporting swallowing questionnaire, clinical swallowing examination, and fibre-optic endoscopic evaluation of swallowing (FEES). Participants with COPD demonstrated impaired LPS defined by elevated laryngeal adductor reflex thresholds and high incidence of pharyngeal residue on FEES. Positive correlations were identified between their clinical swallowing examination and FEES results for the presence of laryngeal penetration/aspiration (p < 0.04), vallecular residue (p < 0.01), and piriform residue (p < 0.01). In conclusion, COPD patients have reduced laryngopharyngeal mechanosensitivity and impaired swallowing function characterized primarily by pharyngeal stasis. The combination of these deficits may place patients with COPD at increased aspiration risk due to lack of detection of pharyngeal residue and subsequent inhalation of pharyngeal contents.

The effect of chronic obstructive pulmonary disease on laryngopharyngeal sensitivity.

Patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of aspiration secondary to impaired swallow function. One possible cause of this impairment is a reduction in laryngopharyngeal sensitivity. The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. We conducted a study to investigate the effect of COPD on laryngopharyngeal sensitivity by using laryngopharyngeal sensory discrimination testing (LPSDT). Our study population was made up of 20 adults (mean age: 71.7 yr) with clinically proven COPD and 11 healthy, age-matched controls. All 31 subjects underwent LPSDT with the use of an air-pulse stimulator via a nasendoscope. The threshold of laryngopharyngeal sensation was evaluated by measuring the amount of air pressure required to elicit the laryngeal adductor reflex (LAR). We found that the patients with COPD had a significantly higher LAR threshold than did the controls (p< 0.001). We conclude that patients with COPD have significantly less mechanosensitivity in the laryngopharynx. This sensory change may place patients with COPD at increased risk for aspiration.

Left atrial compression and the mechanism of exercise impairment in patients with a large hiatal hernia.

OBJECTIVES: The purpose of this study was to determine the association between cardiac compression and exercise impairment in patients with a large hiatal hernia (HH). BACKGROUND: Dyspnea and exercise impairment are common symptoms of a large HH with unknown pathophysiology. Studies evaluating the contribution of cardiac compression to the pathogenesis of these symptoms have not been performed. METHODS: We collected clinical data from a consecutive series of 30 patients prospectively evaluated with resting and stress echocardiography, cardiac computed tomography, and respiratory function testing before and after laparoscopic HH repair. Left atrial (LA), inferior pulmonary vein, and coronary sinus compression was analyzed in relation to exercise capacity (metabolic equivalents [METs] achieved on Bruce treadmill protocol). RESULTS: Exertional dyspnea was present in 25 of 30 patients (83%) despite normal mean baseline respiratory function. Moderate to severe LA compression was qualitatively present in 23 of 30 patients (77%) on computed tomography. Right and left inferior pulmonary vein and coronary sinus compression was present in 11 of 30 (37%), 12 of 30 (40%), and 26 of 30 (87%) patients, respectively. Post-operatively, New York Heart Association functional class and exercise capacity improved significantly (number of patients in New York Heart Association functional classes I, II, III, and IV: 6, 11, 11, and 2 vs. 26, 4, 0, and 0, respectively, p < 0.001; METs [percentage predicted]: 75 ± 24% vs. 112 ± 23%, p < 0.001) and resolution of cardiac compression was observed. Absolute change in LA diameter on the echocardiogram was the only independent cardiorespiratory predictor of exercise capacity improvement post-operatively (p = 0.006). CONCLUSIONS: We demonstrate, for the first time, marked exercise impairment and cardiac compression in patients with a large HH and normal respiratory function. After HH repair, exercise capacity improves significantly and correlates with resolution of LA compression.

Laparoscopic repair of large hiatal hernia: impact on dyspnoea.

INTRODUCTION: This study aims to examine the impact of laparoscopic repair of large hiatal hernia on dyspnoea severity, respiratory function and quality of life. METHODS: From 2004 to 2008, 30 consecutive patients with large para-oesophageal hernia defined as >50% of stomach in the intra-thoracic cavity and minimum follow-up of 2 years were included in this study. All patients had a formal respiratory function test 1 week prior and 3 months after their laparoscopic hiatal hernia repair. Patients rated symptom severity and completed a quality-of-life questionnaire [Gastrointestinal Quality of Life Index (GIQLI)] pre-operatively, and post-operatively at 3 months, 6 months and yearly thereafter. RESULTS: There was no hospital mortality, and the morbidity rate was 10%. In 26 patients with pre-operative dyspnoea, 22 had complete resolution while the remaining 4 had improvement of dyspnoea severity post-operatively. The mean dyspnoea severity index reduced from 2.4 to 1.3 (P < 0.001). Overall, there was 1%, 3% and 3% post-operative increase in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) values for the whole group, none of which reached statistical significance. For patients with resolution or improvement of dyspnoea after laparoscopic repair, no significant change of respiratory function parameters was demonstrated. GIQLI score improved from a pre-operative value of 85.7 to 107.9 post-operatively (P < 0.001). CONCLUSIONS: We failed to show a significant change in post-operative respiratory function despite clearly demonstrated improvement of respiratory symptoms. Alternative explanations for reduction of dyspnoea severity should be sought.

Effect of unilateral endobronchial valve insertion on pulmonary ventilation and perfusion: a pilot study.

BACKGROUND AND OBJECTIVE: The effects of bronchoscopic lung volume reduction (BLVR) on pulmonary ventilation and perfusion are incompletely understood. In this pilot trial, we investigated serial changes in regional ventilation and perfusion following unilateral endobronchial valve placement in COPD patients with heterogeneous emphysema. METHODS: At baseline and at days 30 and 90 following BLVR, subjects underwent lung function, 6MWD and St George's Respiratory Questionnaire. Ventilation and perfusion scintigraphy were performed to quantitate and serially compare regional differences. RESULTS: Six out of eight subjects completed the study; all had endobronchial valves targeting their left upper lobe. At day 90 post-BLVR, there was a trend towards an increase in FEV(1) and a mean reduction in St George's Respiratory Questionnaire score of nine units. In the targeted left upper zone there was reduced ventilation and perfusion. Ventilation and perfusion to the right lung; and specifically the right lower zone, significantly increased. CONCLUSIONS: There appears to be redistribution of ventilation and perfusion to the contralateral lung following endobronchial valve placement. This may be of importance when assessing patients for unilateral BLVR. Selecting patients with heterogeneous disease is emphasized, taking into consideration not just comparison between upper and lower lobes, but between left and right lungs. A larger trial is currently underway, guided by these findings.

Obstructive sleep apnoea: a cause of chronic cough.

Chronic cough is a common reason for presentation to both general practice and respiratory clinics. In up to 25% of cases, the cause remains unclear after extensive investigations. We report 4 patients presenting with an isolated chronic cough who were subsequently found to have obstructive sleep apnoea. The cough improved rapidly with nocturnal continuous positive airway pressure therapy. Further studies are required to investigate the prevalence of coexistence of these common conditions.

Autosomal dominant hereditary sensory neuropathy with chronic cough and gastro-oesophageal reflux: clinical features in two families linked to chromosome 3p22-p24.

Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.