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Novità nella Terapia delle Malattie Respiratorie Novembre 2014.

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Presentation on theme: "Novità nella Terapia delle Malattie Respiratorie Novembre 2014."— Presentation transcript:

1 Novità nella Terapia delle Malattie Respiratorie Novembre 2014

2 Novità nella Terapia delle Malattie Respiratorie Wheezing prescolare Tosse Infezioni Wheezing prescolare

3 Wheezing episodico virale Wheezing da fattori multipli Mantenimento consigliato sempre un trial terapeutico, sospendere se inefficace  Antileucotrienico, oppure  CSI, oppure  CSI + antileucotrienico  Antileucotrienico, oppure  CSI, oppure  CSI + antileucotrienico  CSI (es. beclometasone equivalente 400 μg/die per 3 mesi) se sintomi persistenti:  CSI + antileucotrienico  CSI (es. beclometasone equivalente 400 μg/die per 3 mesi) se sintomi persistenti:  CSI + antileucotrienico Wheezing in età prescolare: terapia © 2013 PROGETTO LIBRA Brand Eur Respir J. 2014

4 OR for long-term ICS and/or leukotriene modifiers prescription Frequent wheeze ED visits Personal allergy Day-care diseases attendance 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Terapia di mantenimento nel wheezing prescolare: in base a cosa decidere? Terapia di mantenimento nel wheezing prescolare: in base a cosa decidere? What drives prescribing of asthma medication to preschool wheezing children? Montella, Pediatr Pulmonol pts (32.8 mo) with wheezing ( 54% frequent wheeze: ≥ 4 episodes/yr)

5 77% 23% Frequenza e severità dei sintomi sono i principali determinanti nella decisione dei pediatri di libera scelta di trattare o non trattare a lungo termine p < 0.05 p = NS 23% 77% What drives prescribing of asthma medication to preschool wheezing children? Montella, Pediatr Pulmonol 2013

6 Eur Respir J. 2014

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8 Novità nella Terapia delle Malattie Respiratorie Tosse

9 Duration of symptoms of respiratory tract infections in children: systematic review. Thompson, BMJ Days Resolution of acute cough in 50% of ch. at 10 days 10%: cough at 25 days 50 % 10

10 Starting point for treatment of cough: Medical History  Acute (< 3 wks)  Recurrent acute (≥ 2/yr; 7-14 days)  Chronic (> 8 wks)  Prolonged acute (subacute; 3-8 wks) Marais, ADC 2005 ACUTE and SUB-ACUTE CHRONIC RECURRENT Therapy for cough should be directed at the aetiology and specific treatments used where possible Chung, Pulm Pharmacol Ther 2002

11 ACUTE COUGH  Foreign Body  urgent rigid bronchoscopy HOW TO TREAT? EZIOLOGIA specifica se ne è chiaramente identificabile la causa (ad es. se associata a caratteristiche suggestive di una patologia polmonare o sistemica) non specifica quando è isolata, senza evidenza di altri sintomi respiratori ed associata a rx- torace nella norma Shields, Thorax 2008  Respiratory tract infection  Non Specific Cough.

12 Honey, Dextromethorphan (DM), and No Treatment on Nocturnal Cough for Coughing children and Their Parents. Paul, Arch Pediatr Adolesc Med 2007 Honey may be preferable for cough and sleep difficulty in URTI 105 ch. with URTI & night cough Cough frequency First night Second night p< Score Over-The-Counter (OTC) drugs Decongestionants Expectorans Antihistamines Antitussives Dextromethorphan Codeine Non drugs (honey)

13 Treating cough and cold: Guidance for caregivers of children and youth. Goldman, Paediatr Child Health 2011  Fluid intake Mainstay of therapy  Humidified air, Echinacea, Zinc, Vitamin C Frequently used, not recommended  Non steroidal anti-inflammatory drugs Not significantly reduce symptom score/duration may affect discomfort caused by the viral illness  Antihistamines No clinically significant effect  Honey Pasteurized honey safe in > 1 yr Demulcent/antioxidant/antimicrobial effects/increases cytokines

14 2010 Azione antiossidante antiinfiammatoria anestetica antinfettiva

15 Mucolitici Controindicazione in età < 2 aa (aumento di tosse/muco, dispnea, vomito) * Per età > 2 aa, l'uso di un mucolitico è possibile, ma non va continuato in caso di persistenza o peggioramento dei sintomi. Alcune significative misure in grado di dar sollievo: Far dormire in posizione supina, con la testa sollevata Far bere il bambino frequentemente Tenere fresca la stanza Non fumare in casa, anche al di fuori della camera Acetilcisteina, carbocisteina, ambroxolo, bromexina, sobrerolo, neltenexina, erdosteina, telmesteina * Farmaci uso rettale con derivati terpenici (es, canfora, timo, terpineolo, mentolo, olii di aghi di pino, eucalipto e trementina): NO < 30 mesi e se epilessia/conv. febbrili) Novembre 2010 Mucolitici per uso orale/rettale

16 Upper Airway Cough Syndrome (UACS) in Children Includes various types of rhinosinus diseases that induce cough (allergic/nonallergic rhinosinusitis; tonsillar hypertrophy) Antihistamines/ nasal steroids + allergen avoidance (= allergic rhinitis) Resolution can take up to 2- 4 wks of therapy Goldsobel, J Pediatr 2010 PROLONGED ACUTE ( SUBACUTE ) COUGH 3-8 wks

17 Chest 2006 Thorax 2008 CHRONIC COUGH Chronic sinus disease? Protracted Bacterial Bronchitis? SPECIFIC COUGH

18 Protracted Bacterial Bronchitis in which patients? Preschool healthy children with significant viral LRT infections H. influenzae S. pneumoniae M. catarrhalis P. aeruginosa Priftis, Chest 2013 Chronic wet cough ≥ 4 wks in the absence of other diagnoses Persistent symptoms + intermittent exacerbations Impairment of host defenses and impaired mucociliary clearance CILIA CHANGES  RECOVERY AFTER MANY WEEKS CHEST IMAGING Normal lung (30%) Bronchial wall thickening (48%) Increased bronchial markings (20%) Consolidation (14%) Narang, PLoS One. 2014

19 Chronic Sinusitis Oral antibiotic therapy Scadding, CEA 2007 Protracted Bacterial Bronchitis (PBB) Oral antibiotic therapy + Chest physiotherapy Priftis, Chest 2013 Kompare, J Pediatr 2012 CHRONIC COUGH

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21 Infezioni Novità nella Terapia delle Malattie Respiratorie

22 1.Clinicians should not administer salbutamol 2.Clinicians should not administer epinephrine 3.Nebulized hypertonic saline should not be administered in the ED 4.Clinicians may administer nebulized hyper. saline (3%) in hospital 5.Clinicians should not administer systemic steroids in any setting 6.Clinicians may choose not to administer O 2 if SaO 2 > 90% 7.Clinicians may choose not to use continuous pulse oximetry 8.Clinicians should not use chest physiotherapy 9.Clinicians should not administer antibacterial medications to infants and children unless there is a concomitant bacterial infection, or a strong suspicion of one 10.Clinicians should administer nasogastric or intravenous fluids for infants who cannot maintain hydration orally Pediatrics.Pediatrics Nov

23 Changes in gastric and lung microflora with acid suppression. Rosen, JAMA Pediatr Oct 5yr prospective study of 99 pts 1-18 yrs (cough at least 3 times/wk for at least 1 month  broncho/gastroscopy; 48% acid suppressed) p < 0.05 Gastric bacterial concentrations, log 10 CFU/ml Bacillus; Dermabacter; Lactobacillus; Peptostreptococcus; Capnocytophaga; Propionibacterium Positive correlations between proximal nonacid reflux & lung bacterial concentrations (r  0.5!) Lung Gastric flora can influence lung flora through nonacid GER in acid-suppressed patients Acid suppression may need to be limited in patients at risk for infections

24 Oral Amoxicillin: 1° choice: effective, tolerated, cheap Alternatives: co-amoxiclav, cefaclor, macrolides Macrolides: -add if no response to 1 st line therapy after 48 h (see severity assessment) -use if Mycoplasma/Chlamydia is suspected Pediatric CAP: which antibiotic should be used? Thorax 2011, CID 2011

25 Parenteral therapy Preferred: intravenous azithromycin (10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible) Alternatives: intravenous erythromycin lactobionate (20 mg/kg/d every 6 hours) Oral therapy (step-down therapy or mild infection) Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/d once daily on days 2–5) Alternatives: clarithromycin (15 mg/kg/d in 2 doses) or oral erythromycin (40 mg/kg/d in 4 doses); INPATIENTS Management of Atypical Bacteria Macrolides at least x 14 days (azithro 5 days) OUTPATIENTS CID 2011

26 Erythromycin interacts with motilin receptors, induces strong gastric and pyloric bulb contractions  infantile hypertrophic pyloric stenosis (3 to 12 wks old infants: 1-2 % o births) 5 giorni di terapia per un bambino di 15 Kg: claritromicina ~ € 16 azitromicina ~ € 22 eritromicina ~ € 10 PEARLS

27 Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis. Lund BMJ Erythromycin is associated with hypertrophic pyloric stenosis risk, but no certainty about other macrolides (pertussis !!!!!)

28 A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma p. in pediatric patients. Matsubara J Infect Chemother % macrolide -sensitive 32% macrolide -resistant Efficacy of macrolide therapy 91.5% for macrolide sensitive 22.7% for macrolide resistance (p < 0.01) In children increasing prevalence of macrolide-resistant M. pneumoniae More prolonged fever (> 48 hr) and cough Macrolide sensitive Macrolide resistent Fever days Cough days

29 F requency of the A2063G mutation in 23S rRNA gene [significantly >> in children (61.3%) than adults (13.3%)] Yoo, Antimicrob Agents Chemother The resistance 30 ch. with Mycoplasma (PCR + serology) 70% resistant (fever) After minocycline, fever disappeared (48 h) Antibiotic Management of Atypical Bacteria Mycoplasma (DNA copies) Kawai Respirology. 2012

30 Clinical Relevance of Mycoplasma macrolide resistance Cardinale, J Clin Microbiology 2013 Levofloxacin in macrolide resistant M. pneumoniae

31 Oral therapy (step-down therapy or mild infection) INPATIENTS Management of Atypical Bacteria Preferred: intravenous azithromycin (10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible) Alternatives: intravenous erythromycin lactobionate (20 mg/kg/d every 6 hours) or levofloxacin (16-20 mg/kg/d every 12 hours; maximum daily dose, 750 mg) OUTPATIENTS Parenteral therapy Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/d once daily on days 2–5) Alternatives: clarithromycin (15 mg/kg/d in 2 doses) or oral erythromycin (40 mg/kg/d in 4 doses); for children >7 yrs old, doxycycline (2–4 mg/kg/day in 2 doses; for adolescents with skeletal maturity, levofloxacin (500 mg) or moxifloxacin (400 mg)/d CID 2011

32 WARNING Bacteria acquire macrolide resistance very fast if used indiscriminately (especially the second-generation agents) Lancet 2007Eur Respir J 2010 S. pneumoniae resistance to macrolides  Italy34% (range, 25-50%)  Southern Italy>70% (2012)

33 Resistenza S. pneumoniae ai macrolidi in Campania (2012) TUTTI I MATERIALI: 61.7% SANGUE e LIQUOR: 63% RESPIRATORI: 61.7% AR-ISS: sorveglianza antibiotico-resistenza in Italia Rapporto del triennio Gram-negativi : ↑↑ resistenza E. coli: fluorochinoloni K. pneumoniae: Italia: 36%!! cefalosporine III^ gen. (37%) fluorochinoloni

34 Can Resistance to Antibiotics Be Minimized? Recommendations 1.Limit the spectrum of activity of antimicrobials to that required to treat the identified pathogen. 2.Use the proper dosage of antibiotics to achieve a minimal concentration to decrease risk of resistance. 3.Treat for the shortest effective duration to minimize exposure of both pathogens and normal microbiota to antimicrobials. 4.Limit exposure to any antibiotic.

35 Sinusitis and Pneumonia Hospitalization After Introduction of PCV. Lindstrand, Pediatrics Nov 10 PCV7PCV13 PCV7 PCV7 and PCV13 prevent pneumonia at preschool age

36 If discovery of new antibiotics continues to falter while resistance to drugs continues to spread, society’s medicine chest will soon lack effective treatments for many infections. Nathan, Sci Transl Med TAKE HOME MESSAGE


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