The Respiratory Tract Diseases

1. The RespiratoryTractDiseases Barbara Tejza

2. BRONCHIOLITIS Bronchiolitis is an acute infective illness of infants whichisconnected withinflammation of the very small airways (bronchioles). It is the most common lower respiratory tract infection in infants. It results in mucosal edema and intraluminal accumulation of mucus and cellular damage. Airway obstruction resulting from swelling leads to inadequate expiratory airflow. Even minor bronchiolar wall thickening significantly affects air flow. Resistance is increased during both inspiration and exhalation but because the radius of an airway is smaller during expiration, obstruction leads to early air trapping and overinflation. If obstruction becomes complete, trapped distal air will be resorbed and the child will develop atelectasis.

3. AETIOLOGY Respiratory syncytial virus (RSV) causes 80% of cases of bronchiolitis. The others are caused by a variety of other respiratory viruses including influenza, parainfluenza, human metapneumovirus, adenovirus, occasionally Rhinoviruses and Mycoplasma pneumonia. RSV is a single-stranded RNA Paramyxovirus. The surface protein are responsible for attachment and penetration the cytoplasm and fusionviralcellwith the host cell. It enables transfer of viralgeneticmaterial and causesformation of syncytia. Thesesyncytia are the hallmark of the RSV cytopathiceffect and arenecessary to cell-to-cellviraltransmision.

4. SYNCYTIA-multinukleate mass of cytoplasmresulting from fusion of cells.

5. VIRUS RSV

6. AETIOLOGY RSV is extremelycontagious and transmitted by direct or close contact with contaminated sectretions. Direct contamination has a higher impact than airborne transmission. The eyes and nose are the most sensitive inoculation area, thus proper handwashing techniques and keeping the hands away from these areas can assist in decreasing transmission. RSV survives on surfaces for several hours. It can survive on the stethoscope for 6 hours on the hands for over 30 minutes. The incubation period is 3-5 days withRSV symptoms peak around day 5 of the illness and often improve at 7-10 days. RSV replicates in the nasopharynx and then binds to the bronchiolar epithelium causing necrosis of the cell. Lymphocytic peribronchiolar infiltration is noted. Interleukins, chemokines and leukotrienes are released and cause inflammation and tissue damage. Recovery of the epithelium starts the first week of the illness but the ciliated cells do not recover until several weeks later.

7. INCIDENCE The virusescause respiratory illness in all age groups but only in infancy the clinical picture of bronchiolitis developes. Most cases occur after the age of 3 months, at a time when maternally derived antibody levels are in decline and an immune system is immature. Infants <2 years are predominantly affected because of the small caliber and increased airways resistance with even mild airway narrowing. Serological surveys suggest that 50% of children have encountered this virus by their first birthday (with a peak age at 2 to 6 months) and 85% by their second birthday-in Europe RSV occurs every year through the winter months-usually from November until the early spring. The incidence falls rapidly between the ages of 1 and 5 years, after which bronchiolitis is uncommon.

8. In the vast majority, bronchiolitis is a self-limiting disease. It is estimated that only 10% of healthy children with bronchiolitis and wheezing require hospitalization, but bronchiolitis is the leading cause of hospitalization of infants younger than age1, and more than 80% of children hospitalized are younger than 6 months of age. The risk of death for a healthy infants with bronchiolitis is less than 0,5%, but the risk is much higher for children with preexisting heart or lung conditions(hemodynamically significant congenital heart disease, bronchopulmonary dysplasia),neuromuscular weakness, immunodeficiency (3-45%).

9. CLINICAL PRESENTATION Initial symptoms are of upper respiratory coryzal illness ( nasal congestion and coryza) which over a few days progresses to give lower respiratory symptoms including tachypnoe, cough and wheezing. Respiratory distress usually develops gradually, typically, the symptoms are worse at night. The tachypnoe may be so severe as to cause feeding difficulties. Low grade fever is usual but not constant. There is usually systemic upset ( irritability) which may reflect the increased work of breathing. Often another family member has a mild upper respiratory tract infection. In contrast to the classic progression of disease, young infants infected by RSV may not have a prodrome and may have apnea as a first sign of infection, mostly pre-term and young neonates. Boys are affected more commonly than girls in a ratio of 1,5:1, and is more common in those children who have not been brest-fed, and in those who live in crowded condition.

10. EXAMINATION Examination will reveal a child with coryzal symptoms and marked tachypnoe with wheeze. The respiratory rate may be 60 to 80 breaths/minute. The expiratory phase is usually prolonged. Breath sounds may be diminished in severe cases. There will often be usage of accessory muscles (intercostal retractions of the lower ribs, suprasternal retractions). Lung hyperinflation and depression of the diaphragm typically result in a palpable liver and spleen. In the more severely infected infants grunting and central cyanosis may be present. During the wheezing phase of illness percussion of the chest usually reveals only hyperresonance Auscultation usually reveals wheeze and extensive areas of fine crackles throughout the breathing cycle and both lung fields. The clinical picture may be variable-wheeze and crackles may come and go.

11. X-RAY Chest radiography typically shows hyperinflation (because of air to be trapped in the distal airway- flattening of diaphragm, horizontal ribs) with patchy, often streaky atelectasis ( subsegmental atelectasis), peribronchial thickenings, increased hilar bronchial markings.

12. The clinicalcourse

13. DIAGNOSIS The diagnosis of bronchiolitis is a clinical one and tests are of little value. In the young infant with the typical clinical presentation the diagnosis is usually straightforward. Routine laboratory tests have not specificity for diagnosing bronchiolitis. A mild leukocytosis of 12,000 to16,000 cells/uL seen frequently but is not specific. Antigen tests (usually by immunofluorescence or ELISA (enzyme-linked immunosorbent assay) or PCR ( polymerase chain reaction) of nasopharyngeal secretions for various viruses are the most sensitive methods to confirm the infection. Identifying the viral agents is helpful for cohorting children with the same infection. Nasopharyngeal swab or washing for RSV may help support diagnosis in some cases.

14. DIFFERENTIALDIAGNOSIS The main differential diagnosis is of a widespread bronchopneumonia. In this case the chest X-ray shows increased shadowing of the lungs fields. This will be helpful in distinguishing bronchopneumonia from bronchiolitis. In older infants, the possibility of asthma with associated upper respiratory viral infection has to be considered-especially if the clinical signs reveals wheeze without crackles and if the there is a positive family history of athopyand asthma.

15. MANAGEMENT Mildly affected children are normally managed by their parents and the general practitioner at home. We have to aware parents of signs of deterioration that include: • poor feeding • irritability • increasing respiratory rate and cyanosis The American Academy of Pediatrics defines severe disease in any child as “signs and symptoms associated with poor feeding and respiratory distress characterized by tachypnea, nasal flaring and hypoxemia. “

16. Indications for hospitalization include: • young age (<6 months old), • premature, cardiopulmonary disease, immunodeficient, • moderate to marked respiratory distress • hypoxemia ( P02< 60 mmm Hg or oxygen saturation <92% on room air) • apnea • inability to tolerate oral feeding • lack of appropriate care available at home

17. Most hospitalized children show marked improvement in 2to 5 days with supportive treatment alone. Bronchiolitis is rarely followed by bacterial superinfection. For infants who are hospitalized supportive care includes: • attention to fluid intake- intravenosus fluids are useful in maintaining hydration in the presence of tachypnea and decreased oral intake • positioning of the infant with the head and neck slightly elevated • frequent nasal suctioning • supplemental humidified oxygen where necessary by nasal cannula • antipyretics Chest physiotherapy is not recommended as no benefits have been identified in clinical trials.

18. It is important to assess oxygenation –monitoring oxygen saturation by pulse oximetry. Frequent, regular assessments and cardiorespiratory monitoring are necessary because respiratory failure may develop very quickly in young infants. Hypoxemia is a consequence of ventilation-perfusion mismatch. The child who goes into respiratory failure needs mechanical ventilation.

19. Systematic reviews conclude than there is little evidence for any drug in treating patients with bronchiolitis. DRUGS • The use of nebulized medications has been studied extensively with variable results. There is no evidence that anti-asthma drugs help in bronchiolitis, though often they are given, particularly ipratropium. • Beta-agonists and anticholinergic therapy may produce only a modest short-term improvement. Nebulized albuterol is not effective in most cases, but nebulized racemic epinephrine in some studies was more beneficial. • The American Academy of Pediatric recommends bronchodilatators should not be used routinely, but may be considered for a trial use and continued if there is an objective response, especially if there is a family history of asthma.

20. Systemic corticosteroids also show variable results in clinical trials. They are not currently recommended for routine use. Some authors say, that systemic corticosteroids have been shown to have an adverse effects in bronchiolitis and are therefore contraindicated. A meta–analysis (Garrison et al) suggests corticosteroids can be effective. Two studies have found that the combination of dexamethasone and salbutamol result in a swifter resolution of bronchiolitis symptoms than either agent alone. In the deteriorating child or the child with preexisting heart or lung disease broadspectrum inhaled antiviral ribavirin is sometimes used, but its effectiveness is at best marginal. Compared with placebo does not reduce rates of respiratory deterioration or death. Ribavirin inhibits the replication of DNA and RNA viruses.

21. Sedatives should not be used. Antibiotics are generally not helpful. Secondary bacterial infections are rare(<1%), thus antibiotics should only be prescribed after certain diagnosis.   Possible effective treatments include the following: • nebulized epinephrine • beta-agonists • ipratropium • corticosteroids • oxygen Treatments of little value include the following: • ribavirin • antibiotic

22. Children who have suffered a severe attack of bronchiolitis in infancy have a tendency torecurrent wheezing episodes which may persist for many years. The mechanism is unclear and seems to be unrelated to the atopic state. The Tucson Children’s Respiratory Study which enrolled more than 1200 children showed, that lower respiratory tract infections increased the risk of wheezing in those up to 6 years of age. After 6 years of age, the incidence decreased and there was no difference found at age 13 years. The cough may linger for about 4 weeks due to a low recovery of the ciliated cells. In adults, RSV was found to alter the airway reactivity for 8 weeks after infection, but returned to normal function at 4 months. Some study shows that IgE is suspected to play the role in wheezing. The more IgE found during the infection, the more wheezing in the child. Children who do not clinically improve as expected should be evaluated for other diagnoses such as vascular ring, heart failure, or foreign body.

23. Recurrence of RSV bronchiolitis is common but tends to be mild and should be treated similarly to the first episode. Rarely, usually following adenovirus infection, the illness may result in permanent damage to the airways ( bronchiolitis obliterans). There is no effective RSV vaccine although there is ongoing work in this field. Earlier attempts at vaccination proved disastrous that immunized children developed a tendency to more severe illness because of enhancement of the immunopathological process which occurs in this disease. Apart from small and limited groups of at-risk children who might benefit from passive protective, there seems to be no effective way of preventing bronchiolitis due to RSV infection in most children.

24. The American Academy of pediatrics currently recommends that monoclonal anti-RSV antibody ( Palivizumab) or RSV immunoglobulin should be given to the following: • infants under 2 years od age with chronic lung disease • preterm infants born< 28 weeks • infants born at 29 to 32 weeks’ gestation when experiencing their first RSV season • infants born at 32-35 weeks who are attending a child care centre, have school-aged siblings, are exposed to environmental pollution, or have abnormalities of the airways or severe neuromuscular problems. This prophylaxis reduces rates of admission to hospital and intensive care. Palivizumab is given monthly intramuscular injections through typical RSV season. Its use is limited mainly by cost. Immunization with influenza vaccine in children above 6 month of age prevent influenza associated bronchiolitis.

25. PULMONARY PHYSIOLOGY The lumen of infant’s airway is narrow and the air way resistance is inversely proportional to the 4th power of the radius so inflammatory processes cause an increase in airway resistance and a significant increase in the work of breathing. The cricoid cartilage encircles the airway just below the vocal cords and is the narrowest portion of the upper airway in children < 10 yr of age.

26. Infants are prone to wheeze owing to a differing set of lung mechanics in comparison to older children and adults. • anatomical distinctions : small caliber of airways, increased resistance of small bronchi, impaired ventilation variant-underdeveloped follicular openings Kohn and bronchial connections Lambert, in preterm infants insufficient and immature surfactant • functional distinctions:barrel chest,very compliant newborn chest wall, the bronchial collapse in the final phase of the exhaust, the high setting of the diaphragm, ribs positioned horizontally, • differences in tracheal cartilage composition and laxity of bones scaffold (skeleton) • immaturity of the immune system-insufficient of secretory Ig A ( the optimal level of IgA about 7 yr of age)

27. It is important to observe the respiratory pattern, rate and degree of effort (work of breathing). Hyperpnea ( increased depth of respiration) may be observed with pulmonary disease and extrapulmonary causes like fever, metabolic acidosis, cardiac disease. Respiratory rates vary with age and activity. Normal rate(breaths/min): Preterm:40-60;term 30-40; 5yr:25, 10yr:20, 15 yr:16;adult:12 Any factor that impairs respiratory mechanism is likely to increase the respiratory rates. Nonrespiratory causes of tachypnea include fever, pain and anxiety.

28. The accessory muscles of inspiration(external intercostal, scalene and sternocleidomastoid muscles) are not used during quiet breathing but are recruited during exercise or in disease states to raise and enlarge the rib cage. When the work of breathing is increased,intercostal, supraclavicular, or substernal retractions are observed. In children, increased respiratory effort is also manifested by nasal flaring and grunting( forced expiration against a partially closed glottis). Exhalation is normally passive but, with active exhalation, the abdominal and internal intercostal muscles are recruited. IllustratedTexbook of PaediatricsFourth Edition T.Lissauer, G.Clayden

29. Respiratory pattern in obstruction of respiratory tract: • mild: reduced rate, increased tidal volume, slightly prolonged expiratory phase • severe: increased rate, increased use of accessory muscles, prolonged expiratory phase

30. Causes of increased work of breathing Increasedinspiratory work we observe in : • -upper airway obstruction (laryngomalacia) • -subglottic narrowing (croup, stenosis) • -decreased pulmonary compliance (pneumonia, pulmonary oedema) Increasedexpiratory work usually indicates intrathoracic airway obstruction

31. Stridor-is a harsh, high-pitched respiratory sound which is usually inspiratory and is produced by turbulent airflow; it isn’t the diagnosis but is a sign of upper airway (extrathoracic) obstruction. The intensity of the stridor does not indicate the degree of severity though severe narrowing will cause stridor during both inspiration and expiration. Many parents describe it as ‘noisy breathing’ or ‘a frightening sound’ when their child cannot catch the breath. Stridor isupperairway –inflammation of upperairway and foreign body

32. Wheezing is produced by partial obstruction of the lower airways and is usually heard more prominently during exhalation but may be present on inspiration. Wheezes can be harsh, monophonic, and low-pitched (usually from large, central airways) or high-pitched and musical (from small peripheral airways).The term wheeze refers to the noise heard either with or without a stethoscope. Wheezesislowerairway- -asthma=expiratorywheezes

33. Rhonchi-irregular sounds which are caused by secretions in the intrathoracic airways Fine crackles or rales- sounds produced by fluid or secretions in small airways, characterisitic of crumpling cellophane. The lack of audible wheezing is not reassuring if the infant shows other signs of respiratory distress, because complete obstruction to airflow can eliminate the turbulence that causes the sounds resonate. Breathsounds in childrenarenormallymoreintense and morebronchial, and expirationismoreprolonged,than in adults. vesicularmurmur vesicularmurmur trachealmurmur bronchialmurmur fine crackles, rales rhonchi stridor wheezing crepitation

34. In the first 5 years of life children have average 6 to 8 episodes of upper respiratory tract infections. The infections occur earlier and more often in those with older siblings and those who attend day care. The vast majority (approx.80%) of respiratory tract infections in young children are mild, self-limiting viral upper respiratory tract infections that require no treatment.

35. PracticalPaediatricsSixth Edition D. M. Roberton, M. South

36. IllustratedTextbok of PaediatricsFourth Edition T. Lissauer, G.Clayden

37. Acute Inflammatory Upper Airway Obstruction (Croup, Epiglottitis, Laryngitis, and Bacterial Tracheitis) Croup The term croup refers to a heterogeneous group of mainly acute and infectious processes that are characterized by a bark-like or brassy cough and may be associated with hoarseness, inspiratory stridor, and respiratory distress. Croup typically affects the larynx, trachea, and bronchi.The term laryngotracheobronchitis refers to viral infection of the glottis and subglottic regions. When the involvement of the larynx is sufficient to produce symptoms, they dominate the clinical picture over the tracheal and bronchial signs. Some clinicians use the term laryngotracheitis for the most common and the most typical form of croup and reserve the term laryngotracheobronchitis for the more severe form which is associated with extension and bacterial superinfection that occurs 5-7 days after the beginning of disease.

38. Traditionally, a distinction has been made between spasmodic or recurrent croup and laryngotracheobronchitis ( acute viral croup). Acute viral croup is a disease of upper airway, and alveolar gas exchange is usually normal. Hypoxia and low oxygen saturation are seen only when complete airway obstruction is imminent Most patient with croup are between the ages of 3 mo and 5 yr, with the peak in the 2ndyr of life. The incidence of croup is higher in boys, it occurs most commonly in the late fall and winter but can occur throughout the year. Recurrences are frequent from 3-6 yr of age and decrease with growth of the airway. Approximately 15% of patients have a strong family history of croup.

39. Croup is caused most commonly by viruses: the parainfluenza viruses(types1,2,and3) account for -75% of cases, influenza A and B, adenowirus, RSV, measles. Mycoplasma pneumonia rarely was isolated from children with croup.

40. Clinical signs: • Most patients have rhinorrhea, pharyngitis, mild cough, low-grade fever for 1-3 days(some children are afebrile) before signs and symptoms of upper airway obstruction become apparent. Physical examination can reveal a hoarse voice, coryza, moderately inflamed pharynx, and slightly increased respiratory rate. • Children develop ”barking” cough, hoarseness, inspiratory stridor. Symptoms are worse at night, they aggravate during crying, and often recur with decreasing intensity for several days and resolve completely within a week. • Older children usually are not seriously ill. Other family members might have respiratory illnesses with laryngitis. • Rarely the upper airway obstruction progresses and needs immediate management.

41. Spasmodic or recurrent croup Spasmodic croup occurs most often in children1-3 yr of age. It is similar to acute laryngotracheobronchitis, except the history of viral prodrome and fever in the patient and family are absent. It is caused mainly by allergic and psychologic factors, although the pathogenesis is unknown. It begins with a sudden onset commonly in the evening or nighttime. The child awakenes with a characteristic barking, metallic cough, noisy inspiration and appears anxious and frightened but without “toxic” signs. Usually, the severity of the symptoms diminishes within several hr, and the following day, the patient appears well except for slight hoarseness and cough. Similar, and usually less severe attacks can occur for another night or 2, usually without extreme respiratory distress.

42. Bacterial Tracheitis (pseudomembranous croup) It is an acute bacterial infection of the upper airway that is potentially live threatening, more common than epiglottitis in vaccinated populations. The mean age is between 5 and 7 yr. It often follows viral respiratory infection (especially laryngotracheitis) so it is considered a bacterial complication of a viral disease, rather than primary bacterial illness.

43. Etiology: Staphylococcus aureus is the most commonly isolated pathogen, also Moraxella catharalis, H.Influenze and anaerobic organism. The major pathologic feature is mucosal swelling at the level of the tricoid cartilage, complicated by thick, purulent secretions, sometimes causing tracheal pseudomembranes. The supraglottis is normal, the distal tracheobronchial trees is unremarkable, in contrast to croup tenacious secretions are seen throughout trachea, and in contrast to bronchitis, the bronchi are not affected.

44. Clinical manifestation: High fever and “toxity”with the respiratory distress can occur immediately or after a few days of apparent improvement. The patient can lie flat, does not drool and does not have dysphagia like in epiglottitis. Treatment: Appropriate antimicrobial therapy which usually includes antistaphylococcals agents: vancomycin and the beta-lactamase resistant beta lactamase agent (e.g.nafcillin or oxacillin). If medical management is not optimal cardiorespiratory arrest, toxic shock syndrome can occur. When bacterial tracheitis is strongly suspected, an artificial airway should be strongly considered ( intubation).

45. Clinical manifestation: High fever and “toxity”with the respiratory distress can occur immediately or after a few days of apparent improvement. The patient can lie flat, does not drool and does not have dysphagia like in epiglottitis. Treatment: Appropriate antimicrobial therapy which usually includes antistaphylococcals agents: vancomycin and the beta-lactamase resistant beta lactamase agent (e.g.nafcillin or oxacillin). If medical management is not optimal cardiorespiratory arrest, toxic shock syndrome can occur. When bacterial tracheitis is strongly suspected, an artificial airway should be strongly considered ( intubation).

46. Acute Epiglottitis (supraglottitis) It is the most dangerous, dramatic, potentially lethal kind of acute inflammatory upper airway obstruction. It is characterized by an rapidly, progressive and potentially fulminating course of high fever, sore throat, dyspnea, and rapidly progressing respiratory obstruction. Often, the healthy child suddenly develops a sore throat and fever. Within a few hours, the patient appears toxic, swallowing and breathing is difficult. Drooling is usually present and the neck is hyperextended in an attempt to maintain the airway. An intensely painful throat prevents the child from speaking or swallowing. Stridor is a late finding and suggest the complete airway obstruction which may cause the death unless adequate treatment is provided. The barking cough typical of croup is rare, usually no other family members are ill with acute respiratory symptomps.

47. The diagnosis requires visualization of a large, cherry red, swollen epiglottis by laryngoscopy, which should be performed in operating room or intensive care unit. Anxiety-provoking interventions such as intravenous line placement, placing the child supine, or direct inspection of the oral cavity should be avoided until the airway is secure.

48. Establishing an airway by nasotracheal intubation, or less often by tracheostomy is indicated because of as many as 6% of children with epiglottitis without an artificial airway die, compared with <1% of those with oral artificial airway. In generally, children are intubated for 2-3 days, because the response to antibiotic is usually rapid. Most patients have concomitant bacteriemia. Fortunatelly, universal use of the H.Influenzae type B vaccine has dramatically reduced the incidence of this disease in children. Other pathogens that may cause epiglottitis include Streptococci, Staphylococci, and Candida albicans.

49. Treatment: All patient should receive oxygen, racemic epinephrine and cortycosteroids are effective. Antibiotics intravenously third-generation cephalosporins: Ceftriaxon, Cefotaxime,or Meropenem.

50. Treatment Treatment of the respiratory distress should take priority over any testing. Most children with spasmodic or infectious croup can be cured safelyat home. Children with croup should be hospitalized for any of the following: • severe stridor at rest • respiratory distress • hypoxia cyanosis • depressed mental status • poor oral intake • need for reliable observation