Selected articles from ATS - 2005 (American Thoracic Society International Meeting) - May 20-25, 2005  

1) Preventing Accidental Ventilator Disconnections in the Tracheostomized Chronic Ventilated Population

C. Bautista, RRCP, L. Watling, RRCP, R. Keslassy, RRCP, D. Renzetti, OT, M. Avendano, MD, Toronto, ON, Canada

Introduction: This study was intended to demonstrate that the use of a ventilator attachment (VentLok®) in combination with staff and patient education can minimize ventilator disconnections in chronically ventilated patients. Methods: Accidental disconnections in 12 chronically ventilated patients were monitored for one year. Results: Number of disconnections were successfully decreased by 90% in 3 months with the use of a ventilator attachment (VentLok®) and education. Conclusions: VentLok® and education were successfully used to diminish the number of unwanted ventilator disconnections in chronic ventilated patients. No adverse events occurred related to VentLok® use.

2) Diaphragm Gene Expression in dy/dy Dystrophic Mice

E. van Lunteren, MD, M. Moyer, MS, P. Leahy, PhD, Cleveland, OH

Primary genetic defects of skeletal muscle elicit a variety of downstream alterations in gene expresssion, which are involved in the genesis of muscle damage or participate in muscle regeneration. Characterizing these changes may identify markers for the severity of muscle damage or provide accessible targets for therapeutic interventions. Data on gene expression are available for dystrophin-deficient mdx mice, but this model is phenotypically very mild compared with human Duchenne muscular dystrophy. The present study examined diaphragm gene expression in a phenotypically more severe model of muscular dystrophy, the merosin-deficient dy/dy mouse, a model of human classical congenital muscular dystrophy. Diaphragm was removed from 8-week old dy/dy and control mice, and gene expression was assessed using Affymetrix gene microarrays. There were >70 genes whose expression averaged at least two-fold different across replicate comparisons in dystrophic compared with normal diaphragm. These included genes encoding contractile protein isoforms (eg. myosin, heavy polypeptide 3, skeletal muscle, embryonic, 119-fold increase), receptors or channels involved in excitation or excitation-contraction coupling (eg. cholinergic receptor, nicotinic, gamma polypeptide, 11.6-fold increase), several procollagen isoforms, and proteins which appear to be involved in cellular adhesion (eg. periostin, osteoblastic specific factor, 6.6-fold increase). Comparison with data from mdx mice (Rouger et al., 2002; Porter et al., 2004) indicates both similarities and differences between the effects of dystrophin and merosin deficiency on diaphragm gene expression, suggesting there are both disease-specific and common downstream events in the primary genetic muscle disorders.

3) Non-Invasive Respiratory Care of Pediatric Neuromuscular Disease (NMD) Patients Following Spine Stabilization Surgery

M.K. Schroth, MD, R. Yngsdal-Krenz, BA RRT, D.C. Mann, MD, Madison, WI

Rationale: NMD patients are at risk for hypoventilation while asleep and poor airway secretion clearance. Scoliosis is a common complication of NMD. Spine stabilization surgery is lengthy and results in patient immobilization for a significant period of time and narcotic pain control. Thus, placing these patients at greater risk for postoperative hypoventilation and poor airway secretion clearance. We evaluated the use of an aggressive non-invasive postoperative respiratory care protocol on patient outcomes. Methods: Since 1999, 19 patients with scoliosis and NMD including spinal muscular atrophy (3-19 years old, n=14), Duchenne or Becker muscular dystrophy (11-17 years old, n=5) had 21 spine surgeries with instrumentation including anterior and/or posterior spinal fusion. Preoperative median FVC was 46% of predicted (range 6-91%). Following surgery, all 19 patients received mechanical insufflation/exsufflation and intrapulmonary percussive ventilation (IPV) through the endotracheal tube every 4 hours. All patients were extubated to non-invasive ventilation per nasal mask. Aggressive airway clearance including IPV, mechanical insufflation/exsufflation, and postural drainage every 4 hours continued. The frequency of respiratory care treatments decreased as the patient tolerated longer periods of time off non-invasive ventilation. Results: All 19 patients tolerated aggressive airway clearance and extubation to non-invasive ventilation. No patient required reintubation or tracheotomy and all patients survived. Patients were extubated one to 15 days after surgery (Median 1 day). Length of stay ranged from 3 to 22 days (Median 7 days). One patient developed ARDS and was intubated for 15 days, then extubated without sequelae. Conclusions: Aggressive non-invasive respiratory care is well tolerated in patients with NMD following spine surgery and may decrease respiratory complications and length of stay.
 

4) Expression and Regulation of CC Class Chemokine Receptors and Ligands in the Dystrophic (mdx) Diaphragm

A. Demoule, MD, M. Divangahi, PhD, G. Danialou, PhD, D. Gvodzic, MD, G. Larkin, W. Bao, MD, B.J. Petrof, MD, Montreal, PQ, Canada

RATIONALE: Although inherited mutations of dystrophin form the genetic basis for Duchenne muscular dystrophy (DMD), secondary mechanisms such as inflammation appear to play a major role in disease pathogenesis. Because CC chemokines orchestrate the recruitment of inflammatory cell types which are found in dystrophic muscles, we wished to study their potential role within the mdx mouse diaphragm model of DMD.
METHODS: Diaphragm and tibialis anterior (TA) muscles were removed from 6, 12 and 24 week old mdx and wild-type BL10 (WT) mice. Muscle infiltration by inflammatory cells was quantified on H&E-stained sections. RNase Protection Assays were performed on the same muscles to quantify expression of chemokine receptors (CCRs 1-5) and ligands (MIP-1α, RANTES). In addition, mdx and WT diaphragm primary cell cultures were stimulated with pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1α).
RESULTS: Muscle inflammation was higher in the mdx diaphragm than in the TA for all age groups. In vivo expression levels of CCRs 1-3 and 5, as well as MIP-1α and RANTES, were significantly higher in the dystrophic group, and were also higher in the diaphragm than in TA. In vitro, only CCR1 was constitutively expressed. However, in vitro stimulation by pro-inflammatory cytokines upregulated CCR1 expression in mdx and WT cultures, and also increased expression of its ligand RANTES to a greater extent in mdx cultures.
CONCLUSIONS: In vivo expression of CC class chemokines and their receptors is higher in the mdx diaphragm than in mdx limb or WT muscles. In addition, there appears to be a greater sensitivity of mdx diaphragm muscle cells to cytokine-induced RANTES upregulation in vitro. These findings suggest a dual mechanism (i.e., upregulation of both receptor and ligand) for boosting CC chemokine effects on the dystrophic diaphragm.
 

5) Self Reported Quality of Life of Adoelscents and Young Adults with Neuromuscular Disease

C.L. DeBrest, MSS, J.R. Chiappa, CRNP, E.M. Hickey, CRNP, S.M. Kolb, CRNP, L.J. Miske, MSN, Philadelphia, PA

BACKGROUND: Respiratory technology has extended the life of patients with neuromuscular disease (NMD). However, few studies have documented the perceived quality of life (QOL) of patients with NMD. Quality of life measurements provide a way to determine the impact of health care when cure is not possible. As health care advances improve physio-functioning, patient satisfaction regarding their life and the effect of technology must be considered.
OBJECTIVE: To report QOL as stated by NMD patients, who are ventilator dependent, between the ages 14 -33 years.
METHODS: A 16 item self-administered questionnaire distributed during the office visit or mailed to patients over the age of 14 years.
TOOL: The Flanagan QOL Scale is a valid and reliable, close-ended questionnaire for people with chronic illness that measures all aspects of life. Domains include 1.) relationships and material well-being, 2.) health and functioning and 3.) personal, social and community commitment. Questions are answered based on a Lickert scale of 1 to 7, with a higher cumulative score (range 16 -112) indicating a better quality of life.
RESULTS: Distributed 34 questionnaires; 17 returned, with participation by 15 patients (44%). Demographics included: 27% with Spinal Muscle Atrophy (SMA), 73% with Duchenne's Muscular Dystrophy (DMD), 33% with non-invasive ventilation, 67% ventilated via tracheostomy, 66% using mechanical in/exsufflator, 60% with gastrostomy tube, 20% female. Mean scores of patients with SMA = 87 (range 74-107) and the mean for patients with DMD =73 (range 50-95).
CONCLUSION: Preliminary data indicates that 93% of adolescents and young adults with NMD report a positive quality of life (score >64). Dependence on multiple forms of technology including ventilation, does not appear to be a significant negative influence in their overall QOL.
 

6) Sleep Disordered Breathing in Myotonic Dystrophy

D.M. Cooper, FRACP,MSc, C.J. Dakin, FRACP, M, P.D. Wales, BHlthSci, G. Williams, BSc, M. Harris, FRACP, Brisbane, QLD, Australia

Background: Myotonic dystrophy (MD), while characterised as a neuromuscular disorder is a multiorgan disorder which also affects the central nervous system (CNS). Neuro-imaging and cognitive testing suggest characteristic CNS changes. Potential problems with sleep breathing in MD are obstruction and hypoventilation due to restriction (from muscle weakness and/or scoliosis) and/or abnormal automatic central control of breathing. Aim: To better characterise the sleep disordered breathing (SDB) of MD. Methods: A retrospective case series review of all children with MD, routinely referred for review of SDB. Data from the clinical review (demographic, genetic, diagnosis) and polysomnographic sleep studies (PSG) (including maximum transcutaneous carbon dioxide levels, minimum oxygen saturation and abnormalities in pattern of breathing). Results: 17 children (12 girls) aged 2.8-17.9 years followed for 3.5 years avg. Infantile onset MD in 9/17. Spirometry normal in 5/14. A degree of hypoventilation was found in 13/17 (76%), ranging from sleep state-related hypercarbia and desaturation to persistent hypercarbia and hypoxia. Of these, 8/13 (62%) had a central apnea hypopnea index (AHI) >5, with non-REM AHI≥ 4 in 4, fig1. Obstructive AHI <5 in all. Bilevel non-invasive ventilation commenced in 5/17(29%). Conclusion: Most children with MD undergoing routine screening PSG had central hypoventilation, with breathing pattern abnormalities in almost half, supporting primary CNS dysfunction as a cause of SDB in MD.

 

7) Sleep Apnea and Daytime Respiratory Function Are Associated with CTG Repeat in Myotonic Dystrophy

P. Begin, MD,PhD, M. Laforte, MD, M. Beaudry, MD, J. Mathieu, MD, L. Laberge, PhD, Saguenay, Montreal, PQ, Canada

Sleep-disordered breathing (SDB), excessive daytime sleepiness (EDS), and lung volume restriction (LVR) are common features in myotonic dystrophy (MD). We seek to document the relationship between these features and the causative gene defect (CTG repeat) in a representative sample from a general MD population. Forty-three patients (CTG: 830±585, age: 50±10 y) underwent polysomnography for two consecutive nights, multiple sleep latency test (MSLT), pulmonary function tests, and answered an Epworth sleep questionnaire. Apnea-hypopnea index (AHI) was found to be 22±14 with 85% of the events being of the obstructive type, mean MSLT sleep latency (SL) was 10±4 min, Epworth score 10±6, total lung capacity (TLC) 80±24%pred, and PaCO₂ 45±6 mm Hg. All 25 subjects with proximal limb weakness had an AHI>5. CTG was found to be significantly related to vital capacity (VC, r = -.60), TLC (r = -.52), inspiratory and expiratory maximal occlusion pressures (r = -.47, -.51), PaCO₂ (r =.31), and AHI (r = .31), but not to SL (r = .07). AHI was also significantly related to body mass index (r = .63), TLC (r = -.44), VC (r = -.40), and expiratory reserve volume (r = -.36), but not to SL (r = .14) nor to Epworth score (r = .21). Finally, PaCO₂ was neither significantly related to SL (r = -.25) nor to Epworth score (r = -.17). We conclude that SDB and LVR are highly prevalent in MD, significantly related, and associated with a high CTG count. However, EDS is neither related to CTG repeat nor to daytime or nocturnal respiratory parameters.
 

8) Rate of Decline of Respiratory Muscle Strenght and Vital Capacity Is Associated with CTG Repeat in Myotonic Dystrophy

P. Begin, MD,PhD, J. Mathieu, MD,MSc, Saguenay, Montreal, PQ, Canada

Respiratory muscle weakness and lung volume restriction are prominent clinical features of myotonic dystrophy (MD). We seek the development of respiratory impairment in response to the causative gene defect: the trinucleotide CTG repeat. We retrospectively analysed the most recent spirometry and respiratory muscle strenght assessment in 200 females and 166 patients with MD ( age = 44±13 y, age at onset of symptoms = 20±11 y) followed in our neuromuscular clinic.Follow-up data for a mean period of 7.5±2.8 years was available in 200 patients. Forced vital capacity (FVC) was found to be 74±19%pred, maximal inspiratory pressure (MIP) 63±28 cm H₂O, and maximal expiratory pressure (MEP) 61±26 cm H₂O. CTG was found to be significantly related to FVC(%) (r =-.48), MIP (r = -.32), and MEP (r = -.37).Multiple regression analysis of all three parameters consistently showed for each gender that an interaction factor (a multiple of age by CTG) was a significant co-factor (p<.0001) and that age alone was no longer. Longitudinal studies showed that the mean rate od decline of FVC in adults was 48 ml. The rate of decline was significantly related to CTG (r = .17, p=.036). We conclude that the rate of decline of lung volumes and respiratory muscle strength in MD is closely related to the causative gene defect.