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LOWER RESPIRATORY TRACT INFECTION 

Lower respiratory tract is the part of the respiratory tract below the vocal cords. While oftenused as a synonym for pneumonia, the rubric of lower respiratory tract infection canalso be applied to other types of infection including lung abscess and acute bronchitis.Symptoms include shortness of breath, weakness, high fever, coughing and fatigue.

Lower respiratory tract infections place a considerable strain on the health budget and aregenerally more serious than upper respiratory infections. Since 1993 there has been a slightreduction in the total number of deaths from lower respiratory tract infection. However in2002 they were still the leading cause of deaths among all infectious diseases, and theyaccounted for 3.9 million deaths worldwide and 6.9% of all deaths that year.[1]

 There are a number of acute and chronic infections that can affect the lower respiratorytract. The two most common infections are bronchitis and pneumonia.[2] Influenza affectsboth the upper and lower respiratory tracts. Antibiotics are often thought to be the first linetreatment in lower respiratory tract infections; however, these are not indicated in viralinfections. It is important to use appropriate antibiotic selection based on the infectingorganism and to ensure this therapy changes with the evolving nature of these infectionsand the emerging resistance to conventional therapies.[3] H. influenzae and M.catarrhalis are of increasing importance in both community acquired pneumonia (CAP) andacute exacerbation of chronic bronchitis (AECB) while the importance of S. pneumoniae isdeclining. It has also become apparent the importance of atypical pathogens such as C.

 pneumoniae, M. pneumoniae andL. pneumophila, in CAP.[3]

Classification

[edit]Bronchitis

Main article: Bronchitis

Bronchitis can be classified as either acute or chronic. Acute bronchitis can be defined asacute bacterial or viral infection of the larger airways in healthy patients with no history of recurrent disease.[2]It affects over 40 adults per 1000 each year and consists of transientinflammation of the major bronchi and trachea.[4] Most often it is caused by viral infectionand hence antibiotic therapy is not indicated in immunocompetent individuals.[5][6] There areno effective therapies for viral bronchitis.[6][7]  Treatment of acute bronchitis with antibiotics iscommon but controversial as their use has only moderate benefit weighted against potentialside effects (nausea and vomiting), increased resistance, and cost of treatment in a self-limiting condition.[4][8] Beta2 agonists are sometimes used to relieve the cough associatedwith acute bronchitis. In a recent systematic review it was found there was no evidence tosupport their use.[6]

Acute Exacerbations of Chronic Bronchitis (AECB) are frequently due to non-infective causesalong with viral ones. 50% of patients are colonised with Haemophilusinfluenzae, Streptococcus pneumoniae or Moraxella catarrhalis.[2] Antibiotics have only beenshown to be effective if all three of the following symptoms are present:-increased dyspnoea, increased sputum volume and purulence. In these cases 500 mg of Amoxycillin orally, every 8 hours for 5 days or 100 mg doxycycline orally for 5 days should

be used.[2]

[edit]Pneumonia

Main article: Pneumonia

Pneumonia. It occurs in a variety of situations and treatment must vary according to thesituation.[7] It is classified as either community or hospital acquired depending on where thepatient contracted the infection. It is life-threatening in the elderly or those who areimmunocompromised.[9][10] The most common treatment is antibiotics and these vary in theiradverse effects and their effectiveness.[9]Pneumonia is also the leading cause of death in

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children less than five years of age.[11] The most common cause of pneumonia ispneumococcal bacteria, Streptococcus pneumoniae accounts for 2/3 of bacteremicpneumonias.[12] A dangerous type of lung infection with a mortality rate of around 25%.[10] For optimal management of a pneumonia patient the following must be assessed;-pneumonia severity (including where to treat e.g. Home, hospital or intensive care),identification of causative organism, analgesia of chest pain, the need for supplemental

oxygen, physiotherapy, Hydration, bronchodilators and possible complications of emphysema or lung abscess.[13]

For community acquired respiratory infections the appropriate use of fluoroquinolones is atherapeutic option. These have been demonstrated to have targeted in vitro activity againstboth the typical and atypical pathogens of interest.[14][15] The newer fluoroquinolones (e.g.,moxifloxacin or gatifloxacin) have extended gram +ve activity and once daily dosing andhence are potential first line in the treatment of lower respiratory tract infections. [3] Howeverit is clinical response that is the best indicators of efficacy and moxifloxacin or gatifloxacinhave been proven to be effective against community acquired respiratory tract infectionsclinically.[16][17]

[edit]Treatment

[edit]Antibiotic Choice

With increased development of drug resistance, traditional empirical treatments arebecoming less effective, hence it is important to base antibiotic choice on isolated bacteriaand sensitivity tests. According to the Cochrane review of antibiotic use in CAP in adults, thecurrent evidence from RCTs is insufficient in order to make evidenced based decisions onthe antibiotic of choice. Further studies are required to make these decisions. [9] For childrenthey found amoxicillin or procaine penicillin to have greater effect than co-trimoxazole forthe treatment of CAP. In hospital settings, penicillin and gentamicin was found to be moreeffective than chloramphenicol, with oral amoxicillin giving similar results to injectablepenicillins.[11] In another review of children with severe pneumonia, oral antibiotics werefound to be as effective as injectable ones without the side effects of pain, risk of infection,or high cost.[18] Also in a Cochrane review azithromycin has been shown to be no better thanAmoxycillin or Amoxycillin with clavulanic acid in the treatment of lower respiratory

infections.

[19]

The AMH list Amoxycillin as first line of AECB and community acquiredpneumonia where as IV azithromycin is first line if high risk of death. If severe hospitalacquired pneumonia it recommends IV gentamicin and ticarcillin with clavulanic acid.[20]

Pathogenesis -pneumonia

 There are no resident bacteria in the lower respiratory tract. The two most commonmeans of acquiring a lower respiratory tract infection is by inhalation andaspiration. Organisms that enter the alveoli are eliminated by alveolar macrophages.Alveolar macrophages are the most important means of eliminating organisms that get inthe alveoli after escaping the defense mechanisms in the upper respiratory tract and therespiratory airways.

Once a microorganism enters the alveoli, it can be opsonized by IgG in the fluid lining thealveoli and then be ingested by the macrophage via their Fc receptors.

1. If there is no specific antibody to the organism present, the macrophage can stillphagocytize the invader using receptors that bind C-reactive protein or complementor by receptors to pathogen-associated molecular patterns (PAMPs). Mannan,lipopolysaccharide, lipoteichoic acid, N–formylated methionine-containing peptides,

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muramyl peptides, and peptidoglycan are all examples of PAMPs, which the alveolarmacrophage can use to phagocytize bacterial invaders.

2. When the microorganism is phagocytized, the macrophage will destroy the organism,if possible, and present microbial antigens on the surface to awaiting B and T cells.

3. Once activated, the B and T cells can produce more antibody and activatemacrophages. Macrophages simultaneously release factors that help carry

polymorphonuclear leukocytes (PMNs) from the bloodstream and initiate aninflammatory response. PMNs, antibodies, and complement components are useful indestroying the “invaders.”

Many bacteria that cause pneumonia can initially survive in the alveoli due to the followingdefense mechanisms.

• Capsule (e.g., S pneumoniae, H influenzae) production prevents phagocytosis by thealveolar macrophage.

• Viruses and Chlamydia invade host cells before the alveolar macrophages canphagocytize them.

• M tuberculosis can survive in alveolar macrophages even after being phagocytized.

If the organisms survive in the alveoli, microbial growth can cause tissue injury, whichstimulates the host to mount an inflammatory response. Tissue injury can occur due toexotoxins produced by a bacterium, cell lysis caused by a virus, or death of alveolarmacrophages and dumping of their lysosomal contents in the alveoli due to growth of anorganism in the phagocyte. Vascular permeability increases, and PMNs arrive at the areawith many of the serum components, attempting to contain and eliminate the organisms.While the microorganisms are damaging the alveoli, other alveolar macrophages are beingrecruited to the area of inflammation. Lymphoid tissue associated with the lungs(mediastinal lymph nodes) becomes enlarged following activation of the B and Tlymphocytes. Chest radiographs may show evidence of mediastinal lymph nodeenlargement in the patient with pneumonia.

 The accumulation of microorganisms, immune cells, and serum components can cause thealveoli to fill and spread to other alveoli that are in close proximity. This inflammatoryresponse is described as an opacity or a consolidation seen on a chest radiograph, and isoften seen in patients with pneumonia caused by S pneumoniae—this type of pneumonia iscalled typical or lobar pneumonia. The inflammatory response to the infection and themicroorganisms produce factors that allow the microorganisms to leave the lung and exertsystemic effects such as fever. Examples of microbial factors that can have systemic effectsinclude endotoxin from gram-negative bacteria resulting in fever and septic shock, and cellwall components of gram-positive bacteria that can lead to fever and septic shock.

Organisms such as M pneumoniae and the influenza virus initially do not cause a largeamount of fluid to accumulate in the alveoli. However, following infection with theseorganisms, inflammation of the interstitial spaces (walls of the alveoli) occurs, resulting ininterstitial or atypical pneumonia. Chest radiographs of patients with this type of pneumoniashow fine granular diffuse infiltrates.

Other organisms such as Staphylococcus aureus, gram-negative rod-shaped bacteria, andanaerobic bacteria produce abscesses or microabscesses. In these infections the immunesystem can wall off the organisms and produce localized abscesses or microabscesses thatusually show well-defined circular lesions with necrotic translucent centers on chestradiographs.

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Kawasaki disease

From Wikipedia, the free encyclopedia

Kawasaki disease (KD), also known as Kawasaki syndrome, lymph nodesyndrome and Mucocutaneous lymph node syndrome,[1] is anautoimmune disease thatmanifests as a systemic necrotizing medium-sized vessel vasculitis and is largely seen in

children under 5 years of age. It affects many organ systems, mainly those includingthe blood vessels, skin, mucous membranes and lymph nodes; however, its most seriouseffect is on theheart where it can cause severe coronary artery aneurysms in untreatedchildren. Without treatment, mortality may approach 1%, usually within 6 weeks of onset.With treatment, the mortality rate is less than 0.01% in the U.S.[2] There is often a pre-existing viral infection that may play a role in its pathogenesis.[3] The conjunctival and oralmucosa, along with the epidermis (skin), become erythematous (red andinflamed). Edema is often seen in the hands and feet and the cervical lymph nodes are oftenenlarged. Also, a remittant fever, often 40℃ (104°F) or higher, is characteristic of the acutephase of the disease.[4] In untreated children, the febrile period lasts on averageapproximately ten days, but may range from 5 to 25 days. [4] The disorder was first describedin 1967 by Dr. Tomisaku Kawasaki in Japan.[5]

[edit]Classification

Systemic vasculitis is an inflammatory condition affecting both veins and arteries throughoutthe body, and is usually caused by a proliferation of cells associated withan immune response to apathogen, or autoimmunity.[6] Systemic vasculitides may beclassified according to the type of cells involved in the proliferation, as well as the specifictype of tissue damage occurring within the vein or arterial walls. [6] Under this classificationscheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing vasculitis(also called necrotizing angeititis), which may be identifiedhistologically by the occurrenceof necrosis (tissue death), fibrosis, and proliferation of cells associated with inflammation inthe inner layer of the vascular wall.[6][7] Other diseases featuring necrotizing vasculitisinclude Polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura and Churg-Strauss syndrome.[6] Kawasaki disease may be further classified as amedium-sized-vessel vasculitis, affecting medium and small sized blood vessels,[8][9][10] such

as the smaller cutaneous vasculature (veins and arteries in the skin) that range from 50 to100µm in diameter.[11][12] KD is also considered to be a primary childhood vasculitis, adisorder associated with vasculitis that mainly affects children under the age of 18. [13][14] Arecent, consensus-based evaluation of vasculitides occurring primarily in children resulted ina classification scheme for these disorders, to both distinguish them and suggest a moreconcrete set of diagnostic criteria for each.[14] Within this classification of childhoodvasculitides, Kawasaki disease is, again, a predominantly medium-sized vessel vasculitis.[14]

It is also an autoimmune form of vasculitis,[4] and is not associated with ANCA antibodies,unlike other vasculitic disorders associated with them, such as wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome.[6][15] Thiscategorization is considered essential for appropriate treatment.[16]

[edit]Signs and symptoms

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(A) Bilateral, non-exudative conjunctivitis with perilimbal sparing - "conjunctival injection".(B) Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding.(C)Erythematous rash involving perineum. (D) Erythema of the palms, which is oftenaccompanied by painful, brawny edema of the dorsa of the hands. (E) Erythema of the soles,and swelling dorsa of the feet. (F) Desquamation of the fingers. (G) Erythema and induration

at the site of a previous vaccination with Bacille Calmette-Gurin (BCG). (H) Perianalerythematous desquamation.[4]

Kawasaki disease often begins with a high and persistent fever that is not very responsive tonormal treatment withparacetamol (acetaminophen) or ibuprofen.[17][18] The fever maypersist steadily for up to two weeks and is normally accompanied by irritability.[17][18] Affectedchildren develop red eyes because of non-suppurative conjunctivitis,iritis[19] and bilateralanterior uveitis.[20] Inflammation of the mucous membranes in the mouth,[4] alongwith erythema(redness), edema (swelling) with fissures (cracks in the lipsurface), desquamation (peeling) and exsudation of the lipsare also evident. The oropharynx mucosa has enanthema and the tongue maintains an unusual redappearance termed "strawberry tongue" (marked erythema with prominent gustative papillae).[12] Keratic precipitates (detectable by a slit lamp but usually too small to be seen

by the unaided eye), and swollen lymph nodes may also be present and can be the firstmanifestation of the disease.[17][21] Rashes occur early in the disease, and the cutaneous rashobserved in patients with KD is non-specific, polymorphic, non-itchy and normally observedup to the 5th day of fever. Cutaneous exanthema may comprise macular-papular erythematous and fissure lesions, the most common type, in additionto urticariform type rash, purpuric, multiform-like erythema.[22] and peeling of the skin inthe genital area, hands, and feet (especially around the nails and on the palms and soles)may occur in later phases.[17][23] Some of these symptoms may come and go during thecourse of the illness. It is a syndrome affecting multiple organ systems, and in the acutestage of KD, systemic inflammatory changes are evident in many organs.[9]Myocarditis,[24] pericarditis, valvulitis, aseptic meningitis, pneumonitis, lymphadenitis, and hepatitis maybe present and are manifested by the presence of inflammatory cells in the affected tissues.[9] If left untreated, some symptoms will eventually relent, but coronary artery aneurysmswill not improve, resulting in a significant risk of death or disability due to myocardial infarction (heart attack).[12] If treated in a timely fashion, this risk can be mostly avoided andthe course of illness cut short.[25]

Less common manifestations

Syst Manifestations

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em

GIT

Diarrhea, abdominal pain, vomiting, liver dysfunction,pancreatitis, Hydropsgallbladder, cholangitis,intussusception, intestinal pseudo-obstruction, ascites,splenic infarction.

MSS Polyarthritis and arthralgia.

CVSMyocarditis, pericarditis, valvular heart disease.

GUUrethritis, prostatitis, cystitis, priapism, Interstitial nephritis,orchitis, nephrotic syndrome.

CNSAseptic meningitis, and sensorineural deafness.

RSInfluenza-like illness, plural effusion, Atelectasis.

SkinErythema and induration at BCG vaccinesite, Beau's lines, and finger gangrene.

Source: review,[12] table.[26]

High-grade fever (greater than 39 °C or 102 °F; often as high as 40 °C or 104 °F),[12] The duration of fever is on average one to two weeks; in the absence of treatment, itmay extend for three to four weeks.[12] However, when appropriate therapy is started thefever is gone after two days.[17]

Red eyes (conjunctivitis) bilateral without pus or drainage, also known as"conjunctival injection".[19]

Anterior uveitis.[19]

Bright red, chapped, or cracked lips.[12]

Red mucous membranes in the mouth.[12]

Strawberry tongue, white coating on the tongue or prominent red bumps (papillae)on the back of the tongue.[12]

Red palms of the hands and the soles of the feet.[12]

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Peeling (desquamation) palms and soles (later in the illness); peeling may beginaround the nails.[4][17]

Rash which may take many forms, non-specific, polymorphic, non-itchy, butnot vesicle-bullous lesions, and appears on the trunk.[12]

Swollen lymph nodes (frequently only one lymph node is swollen, and is usually ononc side), particularly in the neck area. [23]

 Joint pain (arthralgia) and swelling, frequently symmetrical, Also arthritis can occur.[12]

Irritability.[12]

 Tachycardia (rapid heart beat).[12]

Beau's lines (transverse grooves on nails).[12]

May find breathing difficult.[12]

[edit]Complications

X-ray showing Aneurysmal enlargement of thecoronary arteries, which is the most feared

complication in a Kawasaki syndrome

 The cardiac complications are the most important aspect of the disease. Kawasaki diseasecan cause vasculitic changes (inflammation of blood vessels) in the coronary arteries andsubsequent coronary artery aneurysms. These aneurysms can lead to myocardial infarction (heart attack) even in young children. Overall, about 10–18% of children withKawasaki disease develop coronary artery aneurysms with much higher prevalence amongpatients who are not treated early in the course of illness. Kawasaki disease and rheumatic fever are the most common causes of acquired heart disease among children in the UnitedStates.[27][28]

[edit]Causes

Like all autoimmune diseases, the cause of Kawasaki disease is presumably the interaction

of genetic and environmental factors, possibly including an infection. The specific cause isunknown,[29][30][31] but current theories center primarily on immunological causes for thedisease. Evidence increasingly points to an infectious etiology,[32] but debate continues onwhether the cause is a conventional antigenic substance or a superantigen.[33]Children's Hospital Boston reports that "[s]ome studies have found associations between theoccurrence of Kawasaki disease and recent exposure to carpet cleaning or residence near abody of stagnant water; however, cause and effect have not been established."[28]

An association has been identified with a SNP in the ITPKC gene, which codesan enzyme that negatively regulates   T-cell activation.[34] An additional factor that suggests

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genetic susceptibility is the fact that regardless of where they are living, Japanese childrenare more likely than other children to contract the disease. [28] The HLA-B51 serotype hasbeen found to be associated with endemic instances of the disease.[35]

[edit]Diagnosis

Criteria for Diagnosis of Kawasaki Disease

Fever of ≥5 days' duration associated with atleast 4† of the following 5 changes

Bilateral nonsuppurative conjunctivitis

One of more changes of the mucous membranes of 

the upper respiratory tract, including pharyngeal injection, dry fissured lips,injected lips, and "strawberry" tongue

One or more changes of the extremities, includingperipheralerythema, peripheral edema, periungual desquamation, and generalizeddesquamation

Polymorphous rash, primarily truncal

Cervical lymphadenopathy >1.5 cm in diameter

Disease cannot be explained by some other knowndisease process

†A diagnosis of Kawasaki disease can be made if fever and only 3 changes are present in conjunctionwith coronary artery disease documented by two-

dimensional echocardiography or coronaryangiography.

Source: Nelson's essentials of pediatrics,[36] Review[37]

Kawasaki disease can only be diagnosed clinically (i.e. by medical signs and symptoms). There exists no specific laboratory test for this condition. It is difficult to establish the

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diagnosis, especially early in the course of the illness, and frequently children are notdiagnosed until they have seen several health care providers. Many other serious illnessescan cause similar symptoms, and must be considered in the differential diagnosis,including scarlet fever, toxic shock syndrome,  juvenile idiopathic arthritis, and childhoodmercury poisoning (acrodynia).[citation needed ]

Classically, five days of fever[38] plus four of five diagnostic criteria must be met in order to

establish the diagnosis. The criteria are: (1) erythema of the lips or oral cavity or cracking of the lips; (2) rash on the trunk; (3) swelling or erythema of the hands or feet; (4) red eyes(conjunctival injection) (5) swollen lymph node in the neck of at least 15 millimeters.

Many children, especially infants, eventually diagnosed with Kawasaki disease do not exhibitall of the above criteria. In fact, many experts now recommend treating for Kawasakidisease even if only three days of fever have passed and at least three diagnostic criteriaare present, especially if other tests reveal abnormalities consistent with Kawasaki disease.In addition, the diagnosis can be made purely by the detection of coronary artery aneurysmsin the proper clinical setting.

[edit]Investigations

A physical examination will demonstrate many of the features listed above.

Blood tests

Complete blood count (CBC) may reveal normocytic anemia andeventually thrombocytosis

Erythrocyte sedimentation rate (ESR) will be elevated

C-reactive protein (CRP) will be elevated

Liver function tests may show evidence of hepatic inflammation and low serum albumin

Other optional tests

Electrocardiogram may show evidence of  ventricular dysfunction or,

occasionally, arrhythmia due to myocarditis Echocardiogram may show subtle coronary artery changes or, later, true aneurysms.

Ultrasound or computerized tomography may show hydrops (enlargement) of the gallbladder

Urinalysis may show white blood cells and protein in the urine(pyuria and proteinuria) without evidence of bacterial growth

Lumbar puncture may show evidence of aseptic meningitis

Angiography was historically used to detect coronary artery aneurysms and remainsthe gold standard for their detection, but is rarely used today unless coronary arteryaneurysms have already been detected by echocardiography.

[edit]Treatment

Children with Kawasaki disease should be hospitalized and cared for by a physician who hasexperience with this disease. When in an academic medical center, care is often sharedbetween pediatriccardiology and pediatric infectious disease specialists (although nospecific infectious agent has been identified yet).[28] It is imperative that treatment bestarted as soon as the diagnosis is made to prevent damage to the coronary arteries.

Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease[39] and isadministered in high doses with marked improvement usually noted within 24 hours. If thefever does not respond, an additional dose may have to be considered. In rare cases, a third

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dose may be given to the child. IVIG by itself is most useful within the first seven days of onset of fever, in terms of preventing coronary artery aneurysm.

Salicylate therapy, particularly aspirin, remains an important part of the treatment (thoughquestioned by some)[40] but salicylates alone are not as effective as IVIG. Aspirin therapy isstarted at high doses until the fever subsides, and then is continued at a low dose when thepatient returns home, usually for two months to prevent blood clots from forming. Except for

Kawasaki disease and a few other indications, aspirin is otherwise normally notrecommended for children due to its association with Reye's syndrome. Because childrenwith Kawasaki disease will be taking aspirin for up to several months, vaccinationagainst varicella and influenza is required, as these infections are most likely to causeReye's syndrome.[41]

Corticosteroids have also been used,[42] especially when other treatments fail or symptomsrecur, but in a randomized controlled trial, the addition of corticosteroid to immune globulinand aspirin did not improve outcome.[43] In cases of kawasaki disease refractory to IVIG,cyclophosphamide and plasma exchange have been investigated as possible treatments,with variable outcomes.

 There are also treatments for iritis and other eye symptoms. Another treatment may includethe use of Infliximab (Remicade). Infliximab works by binding tumour necrosis factor alpha.

[citation needed ]

[edit]Prognosis

With early treatment, rapid recovery from the acute symptoms can be expected and the riskof coronary artery aneurysms greatly reduced. Untreated, the acute symptoms of Kawasakidisease are self-limited (i.e. the patient will recover eventually), but the risk of coronaryartery involvement is much greater. Overall, about 2% of patients die from complications of coronary vasculitis. Patients who have had Kawasaki disease should havean echocardiogram initially every few weeks, and then every one or two years to screen forprogression of cardiac involvement.

It is also not uncommon that a relapse of symptoms may occur soon after initial treatmentwith IVIG. This usually requires re-hospitalization and re-treatment. Treatment with IVIG can

cause allergic and non-allergic acute reactions, aseptic meningitis, fluid overload and, rarely,other serious reactions. Overall, life-threatening complications resulting from therapy forKawasaki disease are exceedingly rare, especially compared with the risk of non-treatment.

Hyperreactive Airway Disease

 The terms "reactive airways" and "reactive airways disease" have crept into the clinicallexicon in recent years. They are being used as synonyms for asthma. The terms are widelyused in case presentations involving outpatients and inpatients, and even patients inintensive care units. They are in particular commonly used in the pediatric setting. Theproblem is that "reactive airways" and "reactive airways disease" are highly nonspecificterms that have no clinical meaning. As such, we view these terms as unhelpful and

potentially harmful, and we recommend that they not be  used.

Patients are usually labeled with "reactive airways" if they have a history of cough, sputumproduction, wheeze, or dyspnea. Sometimes, however, the only prompt for a diagnosis of "reactive airways disease" is the possession by the patient of an inhaler  of some sort. Mostoften, physicians who use the terms do not have pulmonary function test results for thepatient. Certainly, it is very rare that patients have had measurement of airway reactivity  tomethacholine, histamine, or hypertonic saline. Therefore, armed only with symptomsreferable to the airway, or with a history  of inhaler use, the doctor will present on rounds or

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write in the chart, in letters, or in discharge summaries that the patient has "reactive airwaysdisease." Unfortunately, this diagnosis often goes unchallenged. In fact, increasingly theterm is beingcommonly used among specialists in pulmonary  medicine.

  The term "reactive airways disease" needs to be distinguished from reactive airwaysdysfunction syndrome (RADS) and from airway hyperreactivity two terms that have value

and meaning in pulmonary 

medicine. RADS is a specific term coined by Brooks andcoworkers (1) in 1985 to describe an asthma-like illness developing after a single exposure tohigh levels of an irritating vapor, fume,  or smoke. Patients with RADS have methacholineairway hyperreactivity, but other pulmonary function tests may or may not beabnormal. Symptoms and airway hyperreactivity can persist for years afterthe incriminatingexposure. RADS differs from occupational asthma  in that it typically occurs after a singleexposure without a preceding period of sensitization. It should be noted that not  all expertsagree that RADS is a real clinical syndrome (2), arguing that the entity is based on casereports that lack control groups and that usually lack preexposure pulmonary functionassessment. However, the weight of current scientific evidence supports RADS as a distinctclinical entity, and the disorder is currently recognized as distinct by the American ThoracicSociety and the American College of Chest Physicians (3).

Airway hyperreactivity is also a specific term that means that the airways are hyperreactiveto a variety of stimuli includingmethacholine, histamine, hypertonic saline, distilled water,exercise, or eucapnic hyperventilation (4). Hyperreactivity in this context means abronchoconstrictor response at "doses" that normally have no bronchoconstrictor effect.Airway hyerreactivity actually encompasses both airway sensitivity (the dose of agonist atwhich the FEV1

 begins to fall) and airway hyperresponsiveness (the slope of the dose-response curve thereafter). Airway hyperreactivity is a characteristicof asthma and to alesser extent of chronic obstructive pulmonary disease (COPD) (5), but has also beendescribed in patients with allergic rhinitis (6), but no asthma, in cystic fibrosis  (7), and evenin irritable bowel disease (8). Thus, although airway hyperreactivity is a highly specific termwith definite meaning, it is not a disease diagnosis; rather it represents a  physiologicalabnormality of the airway. It is, however, an important component of the diagnostic criteriaforasthma.

 The use of the term "reactive airways disease" in part reflects the difficulty with establishinga diagnosis of asthma in some situations. In the pediatric setting, especially in very youngchildren, the diagnosis of asthma may be problematic becausethe history is difficult toobtain, because good quality pulmonary function tests cannot be obtained, or becauseasthma is a diagnosis that carries a negative connotation for the patients. Thus, the  term"reactive airways disease" may be used as a nonspecific term in clinical contexts rangingfrom asthma, to wheezy bronchitis, to viral bronchiolitis, or even to pneumonia. In adultmedicine, we suspect that the term is popular because of instances in which physiciansobtain a history of wheeze, sputum production, or inhaler use, but a formal diagnosis of asthma is not in the patient record. A formal diagnosis of asthma requires documentation of reversible airway obstruction or airway hyperreactvity in the setting of  a typical history of asthma. Frequently, the physiological information is missing or elements of a typical asthma

history are missing. 

In the absence of these findings, physicians will provide a label 

of "reactive airways disease" to convey that the patient has some sort of airway problem.

 The problem with the term reactive airways or reactive airways disease is not just that theyrepresent an annoyance to purists of terminology. The problem is that using the terms mayprovide physicians with a false sense of diagnosis security. Ascribing a label of reactiveairways to a patient may be harmful in this context, because it may prevent work-up of thecause of the symptom complex that led to the diagnosis of reactive airways disease  in thefirst place. These patients may actually have asthma, chronic bronchitis, emphysema, or

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even pneumonia. Treatment usually prescribed  for these specific diseases may or may notbe prescribed if the diagnosis is "reactive airways disease." Overtreatment may also  be aside effect of this diagnosis. We suspect that many patients  with a diagnosis of "reactive

airways disease" receive treatmentwith inhaled -agonists or with inhaled corticosteroids.However, if the patient does not have asthma there is no evidence that  these treatmentsbenefit the patient.

Finally, the terms "reactive airways" and "reactive airways disease" are now making theirway from the clinical lexicon tothe clinical literature. Two recent publications have usedthe term "reactive airway disease" (9, 10). In one instance reactive  airway disease was usedas a summary term to describe patients with asthma and/or COPD; in the other it was usedsynonymously with airway hyperreactivity (10). We find this trend troubling because manypatients considered to have "reactive airways disease" do not have asthma, and the vastmajority of patients with reactive airways have never had their airway reactivity measured.We believe it essential to preserve the integrity of asthma and airway hyperactivityasdiagnostic terms in the clinical literature. In fact, in the  context of clinical research, webelieve the use of the terms"reactive airways" and "reactive airways disease" willcomplicate research on asthma, especially for clinical epidemiologists who are investigatingthe current worldwide epidemic of  asthma.

In summary, at best the diagnostic label "reactive airways disease" is an annoyance to thoseof us who want to maintain diagnostic  clarity in our discipline. At worst, the term representsa form of diagnostic laziness that may case harm topatients.

Asthma, also known as "hyperactive airways," is classified as a reversible obstructiverespiratory disorder. (5) In this disease, smooth muscle dysfunction and airway inflammationcombine to result in airflow obstruction and airway hyper-responsiveness - leading to anarrowing of the airways. Until recently, asthma treatment has focused on the first of thesetwo mechanisms, smooth muscle dysfunction, because it is the one responsible for the mostobvious and dramatic symptom; wheezing. (6)

 There is no scientific explanation why bands of smooth muscle, which are under involuntary

control, surround the bronchial tubes (the tubes carrying air into and out of the body). Forwhat reason would the body desire to cut off its own air supply? Nonetheless, these tinymuscles exist, and an asthmatic is well aware of their presence.

During normal respiration these bands of muscle are relaxed and air is allowed to movefreely. However, in people with asthma these muscles may spasm or tighten, clamping downon the bronchial tubes. This constriction of airflow into and out of the lungs is where anasthmatic gets his characteristic wheeze.

Airflow obstruction in asthma may result from any one of a number of events, withbronchoconstriction being just one of the players. Airway edema, mucus plug formation, andairway remodeling can also all cause airflow obstruction.(7) In fact, within the last ten yearsor so it has become apparent that involuntary constriction of the smooth muscle lining thebronchial tree may not be the primary cause of asthma. A slower-to-develop swelling and

inflammation of the lining of the bronchial tubes has been discovered to play a fundamentalrole in nearly all cases of this disease.

Medications

Salbutamol metered dose inhaler commonly used to treat asthma attacks.

Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms and long-term control medications used toprevent further exacerbation.[113] monteleukast ( singulair) is used as an adjuctive in thetreatment of persistant type asthma and allows the tapering of high dose inhaled steroids. it

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is also effective in mild persistant type asthma but less evidence suggest use in intermittenttype asthma.

Fast acting

Short-acting, selective beta2-adrenoceptor agonists, suchas salbutamol (albuterol USAN), levalbuterol, terbutaline and bitolterol.[citation needed  ]

 Tremors, the major side effect, have been greatly reduced by inhaled delivery, whichallows the drug to target the lungs specifically; oral and injected medications aredelivered throughout the body. There may also be cardiac side effects at higher doses(due to Beta-1 agonist activity), such as elevated heart rate or blood pressure. However,levalbuterol has been shown to have fewer cardiac side effects and significantly moreanti-inflammatory effects on bronchial smooth muscle than its racemic counterpartalbuterol. The question becomes does this justify its 5-10 fold higher cost. Somehospitals start a patient on levalbuterol until symptoms wane and then switch toalbuterol. Patients must be cautioned against using these medicines too frequently, aswith such use their efficiency may decline, producing desensitization resulting in anexacerbation of symptoms which may lead to refractory asthma and death.[citation needed ]

Older, less selective adrenergic agonists, such asinhaled epinephrine and ephedrine tablets, have also been used; the brand PrimateneMist, for example. Cardiac side effects occur with these agents at either similar or lesserrates to albuterol.[114] [115] When used solely as a relief medication, inhaled epinephrinehas been shown to be an effective agent to terminate an acute asthmatic exacerbation.[114][non-primary  source needed ] In emergencies, these drugs were sometimes administered byinjection. Their use via injection has declined due to related adverse effects.[citation needed ]

Anticholinergic medications, such as ipratropium bromide may be used instead.[citation 

needed ] They have no cardiac side effects and thus can be used in patients with heartdisease; however, they take up to an hour to achieve their full effect and are not aspowerful as the β2-adrenoreceptor agonists.[citation needed ]

Long term control

Inhaled glucocorticoids are mainly considered as preventive medications while oralglucocorticoids are often used to supplement treatment of emergent moderate to severeattacks.[116] They should be used twice daily in children with mild to moderate persistentasthma.[117][non-primary  source needed ] A randomized controlled trial has demonstrated the benefitof 250 microg beclomethasone when taken as an as-needed combination inhaler with100 microg of albuterol.[118][non-primary  source needed ]

Long-acting β2-agonists (LABD) are similar in structure to short-acting selective beta2-adrenoceptor agonists, but have much longer side chains resulting in a 12-hour effect.[citation needed ] While people report improved symptom control, these drugs do not replacethe need for routine preventers, and their slow onset means the short-acting dilators arestill be required. In November 2005, the American FDA released a health advisoryalerting the public to findings that show the use of long-acting β2-agonists could lead to aworsening of symptoms, and in some cases death. [119][dead link ]In December 2008, members

of the FDA's drug-safety office recommended withdrawing approval for thesemedications in children. Discussion is ongoing about their use in adults.[120] A recentmeta-analysis of long-acting beta-agonists indicate a danger in asthma with an 2—4 foldincreased risk for asthma hospitalizations and asthma deaths compared with placebo.[121]

Medications are typically provided as metered-dose inhalers (MDIs) in combination withan asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes themedication with air, making it easier to receive a full dose of the drug. A nebulizer may also

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be used. There is no clear evidence, however, that they are more effective than inhalersused with a spacer.