Management of the Symptomatic PCD
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1 Management of the Symptomatic PCD Andrew Bush MD FRCP FRCPCH FERS Imperial College & Royal Brompton Hospital
2 Conflict of Interest AB has no financial or other COI There will be discussion of off-label and unlicensed use of medications
3 Aims of the Presentation I will not be discussing presenting features or diagnosis, nor the extended manifestations of ciliopathy I will present an update on management and monitoring of the upper and lower airway manifestations of PCD I am assuming a familiarity with basic CF management, on which regrettably much of PCD is based
4 Evidence Base For Treatment
5 For all: General respiratory care Full immunisations including pneumococcal; influenza annually 10-valent pneumococcal-haemophilus influenzae protein D conjugate vaccine: RCT in progress, see Trials 2013; 14: 282 Avoidance of pollutants, especially environmental tobacco smoke Exercise and good nutrition
6 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
7 Airway Clearance? Adherence poorer even than CF! Exercise (any) very important, and may be better tolerated Postural drainage for lower lobes in particular? The devices and desires of our own hearts? PEP mask, Acapella, Vest (BUT, Thorax 2013; 68: ) Pharmacology HS, rhdnase, mannitol?
8
9 More Exercise? Improves lung function Improves bone mineral density (CF) Improves general wellbeing (all) Better bronchodilator than β-2 agonists, see Eur Respir J. 1998; 11:
10 Mucolytics? rhdnase: Not useful/harmful in PCD (c.w. CF) Chest 1998;113: , Am J Respir Crit Care Med; 154: Anecdotal evidence of benefit in individuals Hypertonic saline: No data Anecdotal evidence of benefit in individuals Mannitol: No data or anecdotes; very expensive NAC, others: Useless
11 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
12 PCD Microbiology: mucoid Ps aer is a late phenomenon Am J Respir Crit Care Med 2004; 169:
13 Antibiotics Targets: Gram positives (younger children) Gram negatives (older children, adults) Intermittent oral initially; prophylactic AZM if exacerbations Secondary oral prophylaxis for repeat offenders CF eradication protocols for Pseudomonas aeruginosa Intravenous antibiotics intermittently as needed Regular courses for serial offenders
14 Oral Antibiotics Consider choices (bacteriology) Co-amoxyclav Clarithromycin (tend to hold in reserve) Intermittent oral 2-4 weeks with any exacerbation?with any isolate as per CF? Continuous oral?seasonal Recurrent isolates
15 Exacerbations vs. Lung Attacks Exacerbations Relatively benign Minor inconvenience Fully reversible Lung Attacks An emergency to be dealt with May be irretrievable damage Needs a focussed response: why did this happen, how can we prevent it? Thorax 2011; 66: & 367
16 CF Lung Attacks: FEV 1 does Case control study, single centre, not always recover N=104, admission for first pulmonary exacerbation Q: was FEV1 in the 3 months post-treatment within 95% of previous best in prior 6/12? A: 24 (23.1%) did not recover to their former lung function Pediatr Pulmonol 2010; 45: See also Am J Respir Med 2010; 182:
17 PCD Lung Attacks? 30 PCD patients admitted for 2 weeks ivabs, mean age 11.4 years Respond Non-response Respond Non-response N=23 N=7 Only 2 Ps aer +ve Mean increase in FEV 1 was 8.5% CONCLUSION: 7/30 (23%) failed to return to baseline (including both Ps aer +ve) Sunther M, BTS abstract, Winter 2014
18 Bronchiectasis: AZM and lung attacks Indigenous children age 1-8 years, >1 exacerbation in previous year, Bx or CSLD AZM 30 mg/kg once a week (N=45) or placebo (N=44) 902 child months AZM, 875 placebo Reduced exacerbations, more AZM resistance Lancet Resp Med 2013; 1:
19 What does this mean? PCD lung attacks are serious as well; they should merit a focussed response what went wrong? NOT azithromycin for everyone just consider for exacerbators; once weekly dosing attractive AZM resistance unattractive no free lunches! However, MAI is selected for by ICS, not AZM in our CF clinic!
20 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
21 PCD & Asthma? Many mis-diagnosed as asthma, and their asthma meds never stopped Β-2 agonists only if documented reversibility or acutely responsive wheeze ICS not if no acute BDR, and no atopic personal or family history; any therapeutic trial must be short, focussed and (preferably) have objective end-points
22 ICS: Danger! S. Korea, medium burden TB country; 4 year study Nested case-control study, N= adults newly using inhaled medications 4139 diagnosed with TB, matched controls OR for TB with ICS = 1.20 ( ) Risk not seen in OCS users, signal drowned Thorax 2014; 68:
23 What does this mean? Do NOT be scared of appropriately used ICS! They are lifesaving, and life-transforming! Do NOT use ICS as a general airway tonic Systemic steroids are immunosuppressive: so not surprising that topical steroids are also immunosuppressive Also remember COPD pneumonia data, atypical Mycobacterial data (CF, non-cf) Are more potent steroids better? Are they more immunosuppressive? BEWARE PHARMA!
24 Surgery for localized Only if?localised, and probably not even then bronchiectasis? If CXR suggests localised disease, likely HRCT will show more generalized If HRCT suggests localised, FOB likely pus all over the shop If CXR, HRCT, FOB all say surgery, probably still say NO!
25 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
26 PCD Organization of Care The PCD clinic personnel Paediatricians/ adult physicians ENT surgeons, audiology, audiometry Physiotherapists Psychology, social worker Access to infertility clinics Full, detailed assessment of upper and lower airway at each visit
27 PCD Organization of Care The PCD clinic - investigations Spirometry, earlobe saturation,?others Age appropriate hearing tests Sputum/cough swab/cough plate/induced sputum bacteriology More detailed physiological and other respiratory investigations as appropriate
28 PCD and LCI? Requires only passive cooperation (tidal breathing) N 2 washout or SF 6 washinwashout
29 LCI: New Data on Normal Ranges 1. Over age 5-6, ULN of LCI 7.56 satisfactory 2. Infancy and pre-school: need controls/corrections (all LCFC studies recruited contemporaneous controls) ERJ 2013; 41: LCI vs. height LCI vs. age
30 LCI and PCD LCI in CF: cross-sectionally, more sensitive than spirometry or plethysmography, longitudinally becomes abnormal first. Sensitive to HRCT changes PCD LCI in PCD: no real relationship between spirometry and LCI; no relationship with HRCT changes CF Am J Respir Crit Care Med 2013; 188: Thorax 2012; 67: 49-63
31 LCI and PCD: Are, but! 38 PCD patients, years, 70 healthy controls ( years) LCI (N 2 washout), spirometry and HRCT Good correlations between LCI and FEV1, and CT scores and subscores Milder group: 28/38 had normal spirometry Boon M, Thorax 2015, epub
32 PCD & LCI: Unresolved questions Nitrogen washout: no wash-in so accesses parts of the lung that other gases do not reach Tissue nitrogen production? Effects of 100% oxygen on gas mixing? Equipment differences, disease stage differences? CONCLUSION: do not extrapolate between equipment, between washout gases, between diseases and between stages of the same disease
33 PCD: Role of HRCT? N=20 PCD patients (11.6 yr, ) Total score R=-0.02 P=0.9 Spirometry, HRCT 2.3 years ( ) apart Cross-sectionally, HRCT correlated with FEV 1 Longitudinally, no relationship between change in the two tests FEV 1 Z score Bx score R=-0.02 P=0.9 FEV1 could be stable as HRCT deteriorated Pediatr Pulmonol 2012; 47:
34 PCD Prognosis Three centre, 158 PCD children BMI and spirometry recorded annually Z-scores: 1 st BMI 0.1, FEV , FEF H Infl > once 65%, Ps aer 37%, 5% chronically Ps aer infected No effect of infection on spirometry (UNLIKE CF and Ps aer) or age at diagnosis
35 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
36 PCD: Upper airway disease Chronic secretory otitis media Rhinosinusitis Frontal sinus agenesis Polyps: RARE in our clinic OSA: RARE in our clinic
37 PCD and Tympanostomy Tubes 8 children had 36 sets of tubes inserted prior to referral, 3 had 3 sets post referral Complications 10/11 with tubes vs. 1/19 untreated had persistent discharge 5/11 had a perforation (n=4) or tympanosclerosis (n=1) vs. 0/19 untreated
38 PCD and Tympanostomy Tubes Results Hearing loss the same long-term (mean PTA threshold, 20 db) whether tubes were used or not Conclusions Use hearing aids not tympanostomy tubes Clin Otolaryngol 1997; 22: 302-6
39 PCD - ENT Treatment Check hearing (distraction testing PTA) Hearing aids not grommets Ciprofloxacin eardrops for wet ears (Ps aer inevitably present)?nasal and/or sinus douche?fess
40 Long-term hearing in PCD 71/92 children attending RBH PCD clinic analysed Excluded 8 with perforation or drainage 134 ears analysed 91 abnormal on otoscopy Age-appropriate hearing tests Int J Pediatr Otorhinolaryngol 2005; 69:
41 Upper airway treatment: secretions? Sinusitis and upper airway congestion common Nasal douching with saline or HS on as an as required basis Patients will continue only if they see benefit Increasingly used by our physiotherapists (Could be done using a squeezy washing up liquid bottle?)
42 Upper airway treatment: infection? UA (naso-sinal lavage, nasal swab) & LA (sputum, cough swabs) in 70 children (30 male), median age 11.5 yrs (range 1-18) 44 (63%) of UA samples had positive cultures in comparison to 22 (31%) of LA samples.?means what?do what antibiotic sinus rinsing? Microorganism Marsh G, BTS abstract, Winter 2014 UA+, LA+ UA+, LA- UA-, LA+ UA-, LA- Strep pneum H Inf Staph Aureus PA
43 Managing PCD Airway clearance mechanical, pharmacological Airway infection Variable airflow obstruction Monitoring PCD patients The upper airway Summary and conclusions
44 PCD: Summary PCD lags lamentably behind CF; but there is a huge global momentum (e.g. BESTCILIA). Think about joining in General airway health (smoke exposure, exercise, immunisations) is non-controversial All other treatments should be considered as N of 1 trials, and should be focussed, time-limited with preferably objective endpoints. Do not assume that what works for CF works for everyone PCD is NOT a surgical disease! Shoot for the sky your patients should not be deteriorating!
45 Thank you for listening!
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