LOWER RESPIRATORY TRACT INFECTION

Lower respiratory tract is the part of the respiratory tract below the vocal cords. While often
used as a synonym for pneumonia, the rubric of lower respiratory tract infection can
also 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 are
generally more serious than upper respiratory infections. Since 1993 there has been a slight
reduction in the total number of deaths from lower respiratory tract infection. However in
2002 they were still the leading cause of deaths among all infectious diseases, and they
accounted 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 respiratory
tract. The two most common infections are bronchitis and pneumonia.[2] Influenza affects
both the upper and lower respiratory tracts. Antibiotics are often thought to be the first line
treatment in lower respiratory tract infections; however, these are not indicated in viral
infections. It is important to use appropriate antibiotic selection based on the infecting
organism and to ensure this therapy changes with the evolving nature of these infections
and the emerging resistance to conventional therapies. [3] H. influenzae and M.
catarrhalis are of increasing importance in both community acquired pneumonia (CAP) and
acute exacerbation of chronic bronchitis (AECB) while the importance of S. pneumoniae is
declining. 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 as
acute 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 transient
inflammation of the major bronchi and trachea. [4] Most often it is caused by viral infection
and hence antibiotic therapy is not indicated in immunocompetent individuals.[5][6] There are
no effective therapies for viral bronchitis. [6][7] Treatment of acute bronchitis with antibiotics is
common but controversial as their use has only moderate benefit weighted against potential
side 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 associated
with acute bronchitis. In a recent systematic review it was found there was no evidence to
support their use.[6]
Acute Exacerbations of Chronic Bronchitis (AECB) are frequently due to non-infective causes
along with viral ones. 50% of patients are colonised with Haemophilus
influenzae, Streptococcus pneumoniae or Moraxella catarrhalis.[2] Antibiotics have only been
shown 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 the
situation.[7] It is classified as either community or hospital acquired depending on where the
patient contracted the infection. It is life-threatening in the elderly or those who are
immunocompromised.[9][10] The most common treatment is antibiotics and these vary in their
adverse effects and their effectiveness.[9]Pneumonia is also the leading cause of death in
children less than five years of age.[11] The most common cause of pneumonia is
pneumococcal bacteria, Streptococcus pneumoniae accounts for 2/3 of bacteremic
pneumonias.[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 a
therapeutic option. These have been demonstrated to have targeted in vitro activity against
both 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 and
hence are potential first line in the treatment of lower respiratory tract infections. [3] However
it is clinical response that is the best indicators of efficacy and moxifloxacin or gatifloxacin
have been proven to be effective against community acquired respiratory tract infections
clinically.[16][17]
[edit]Treatment

[edit]Antibiotic Choice
With increased development of drug resistance, traditional empirical treatments are
becoming less effective, hence it is important to base antibiotic choice on isolated bacteria
and sensitivity tests. According to the Cochrane review of antibiotic use in CAP in adults, the
current evidence from RCTs is insufficient in order to make evidenced based decisions on
the antibiotic of choice. Further studies are required to make these decisions.[9] For children
they found amoxicillin or procaine penicillin to have greater effect than co-trimoxazole for
the treatment of CAP. In hospital settings, penicillin and gentamicin was found to be more
effective than chloramphenicol, with oral amoxicillin giving similar results to injectable
penicillins.[11] In another review of children with severe pneumonia, oral antibiotics were
found 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 than
Amoxycillin or Amoxycillin with clavulanic acid in the treatment of lower respiratory
infections.[19] The AMH list Amoxycillin as first line of AECB and community acquired
pneumonia where as IV azithromycin is first line if high risk of death. If severe hospital
acquired 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 common
means of acquiring a lower respiratory tract infection is by inhalation and
aspiration. Organisms that enter the alveoli are eliminated by alveolar macrophages.
Alveolar macrophages are the most important means of eliminating organisms that get in
the alveoli after escaping the defense mechanisms in the upper respiratory tract and the
respiratory airways.

Once a microorganism enters the alveoli, it can be opsonized by IgG in the fluid lining the
alveoli 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 still
phagocytize the invader using receptors that bind C-reactive protein or complement
or by receptors to pathogen-associated molecular patterns (PAMPs). Mannan,
lipopolysaccharide, lipoteichoic acid, N–formylated methionine-containing peptides,
 muramyl peptides, and peptidoglycan are all examples of PAMPs, which the alveolar
macrophage 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 activate
macrophages. Macrophages simultaneously release factors that help carry
polymorphonuclear leukocytes (PMNs) from the bloodstream and initiate an
inflammatory response. PMNs, antibodies, and complement components are useful in
destroying the “invaders.”

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

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

alveolar macrophage.
• Viruses and Chlamydia invade host cells before the alveolar macrophages can
phagocytize 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, which
stimulates the host to mount an inflammatory response. Tissue injury can occur due to
exotoxins produced by a bacterium, cell lysis caused by a virus, or death of alveolar
macrophages and dumping of their lysosomal contents in the alveoli due to growth of an
organism in the phagocyte. Vascular permeability increases, and PMNs arrive at the area
with many of the serum components, attempting to contain and eliminate the organisms.
While the microorganisms are damaging the alveoli, other alveolar macrophages are being
recruited to the area of inflammation. Lymphoid tissue associated with the lungs
(mediastinal lymph nodes) becomes enlarged following activation of the B and T
lymphocytes. Chest radiographs may show evidence of mediastinal lymph node
enlargement in the patient with pneumonia.

The accumulation of microorganisms, immune cells, and serum components can cause the
alveoli to fill and spread to other alveoli that are in close proximity. This inflammatory
response is described as an opacity or a consolidation seen on a chest radiograph, and is
often seen in patients with pneumonia caused by S pneumoniae—this type of pneumonia is
called typical or lobar pneumonia. The inflammatory response to the infection and the
microorganisms produce factors that allow the microorganisms to leave the lung and exert
systemic effects such as fever. Examples of microbial factors that can have systemic effects
include endotoxin from gram-negative bacteria resulting in fever and septic shock, and cell
wall 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 large
amount of fluid to accumulate in the alveoli. However, following infection with these
organisms, inflammation of the interstitial spaces (walls of the alveoli) occurs, resulting in
interstitial or atypical pneumonia. Chest radiographs of patients with this type of pneumonia
show fine granular diffuse infiltrates.

Other organisms such as Staphylococcus aureus, gram-negative rod-shaped bacteria, and

anaerobic bacteria produce abscesses or microabscesses. In these infections the immune
system can wall off the organisms and produce localized abscesses or microabscesses that
usually show well-defined circular lesions with necrotic translucent centers on chest
radiographs.
Kawasaki disease
From Wikipedia, the free encyclopedia

Kawasaki disease (KD), also known as Kawasaki syndrome, lymph node

syndrome and Mucocutaneous lymph node syndrome,[1] is anautoimmune disease that
manifests 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 including
the blood vessels, skin, mucous membranes and lymph nodes; however, its most serious
effect is on theheart where it can cause severe coronary artery aneurysms in untreated
children. 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 oral
mucosa, along with the epidermis (skin), become erythematous (red and
inflamed). Edema is often seen in the hands and feet and the cervical lymph nodes are often
enlarged. Also, a remittant fever, often 40℃ (104°F) or higher, is characteristic of the acute
phase of the disease.[4] In untreated children, the febrile period lasts on average
approximately ten days, but may range from 5 to 25 days. [4] The disorder was first described
in 1967 by Dr. Tomisaku Kawasaki in Japan.[5]
[edit]Classification

Systemic vasculitis is an inflammatory condition affecting both veins and arteries throughout
the body, and is usually caused by a proliferation of cells associated with
an immune response to apathogen, or autoimmunity.[6] Systemic vasculitides may be
classified according to the type of cells involved in the proliferation, as well as the specific
type of tissue damage occurring within the vein or arterial walls.[6] Under this classification
scheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing vasculitis
(also called necrotizing angeititis), which may be identifiedhistologically by the occurrence
of necrosis (tissue death), fibrosis, and proliferation of cells associated with inflammation in
the inner layer of the vascular wall.[6][7] Other diseases featuring necrotizing vasculitis
include Polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein
purpura and Churg-Strauss syndrome.[6] Kawasaki disease may be further classified as a
medium-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 to
100µm in diameter.[11][12] KD is also considered to be a primary childhood vasculitis, a
disorder associated with vasculitis that mainly affects children under the age of 18. [13][14] A
recent, consensus-based evaluation of vasculitides occurring primarily in children resulted in
a classification scheme for these disorders, to both distinguish them and suggest a more
concrete set of diagnostic criteria for each.[14] Within this classification of childhood
vasculitides, 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] This
categorization is considered essential for appropriate treatment.[16]
[edit]Signs and symptoms
(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 often
accompanied 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) Perianal
erythematous desquamation.[4]

Kawasaki disease often begins with a high and persistent fever that is not very responsive to
normal treatment withparacetamol (acetaminophen) or ibuprofen.[17][18] The fever may
persist steadily for up to two weeks and is normally accompanied by irritability. [17][18] Affected
children develop red eyes because of non-suppurative conjunctivitis,iritis[19] and bilateral
anterior uveitis.[20] Inflammation of the mucous membranes in the mouth,[4] along
with erythema(redness), edema (swelling) with fissures (cracks in the lip
surface), desquamation (peeling) and exsudation of the lipsare also evident.
The oropharynx mucosa has enanthema and the tongue maintains an unusual red
appearance 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 first
manifestation of the disease.[17][21] Rashes occur early in the disease, and the cutaneous rash
observed in patients with KD is non-specific, polymorphic, non-itchy and normally observed
up to the 5th day of fever. Cutaneous exanthema may comprise macular-
papular erythematous and fissure lesions, the most common type, in addition
to urticariform type rash, purpuric, multiform-like erythema.[22] and peeling of the skin in
the 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 the
course of the illness. It is a syndrome affecting multiple organ systems, and in the acute
stage of KD, systemic inflammatory changes are evident in many organs. [9]Myocarditis,
[24]
pericarditis, valvulitis, aseptic meningitis, pneumonitis, lymphadenitis, and hepatitis may
be 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 aneurysms
will 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 and
the course of illness cut short.[25]

Less common manifestations

Syst Manifestations
em

Diarrhea, abdominal pain, vomiting, liver

dysfunction,pancreatitis, Hydrops
GIT gallbladder, cholangitis,intussusception, intesti
nal pseudo-obstruction, ascites,splenic
infarction.

MSS Polyarthritis and arthralgia.

Myocarditis, pericarditis, valvular heart

CVS
disease.

Urethritis, prostatitis, cystitis, priapism, Intersti

GU
tial nephritis,orchitis, nephrotic syndrome.

Aseptic meningitis, and sensorineural

CNS
deafness.

Influenza-like illness, plural

RS
effusion, Atelectasis.

Erythema and induration at BCG vaccine

Skin
site, 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, it
may extend for three to four weeks.[12] However, when appropriate therapy is started the
fever 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]
  Peeling (desquamation) palms and soles (later in the illness); peeling may begin
around the nails.[4][17]
 Rash which may take many forms, non-specific, polymorphic, non-itchy, but
not vesicle-bullous lesions, and appears on the trunk.[12]
 Swollen lymph nodes (frequently only one lymph node is swollen, and is usually on
onc 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 disease
can cause vasculitic changes (inflammation of blood vessels) in the coronary arteries and
subsequent coronary artery aneurysms. These aneurysms can lead to myocardial
infarction (heart attack) even in young children. Overall, about 10–18% of children with
Kawasaki disease develop coronary artery aneurysms with much higher prevalence among
patients 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 United
States.[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 is
unknown,[29][30][31] but current theories center primarily on immunological causes for the
disease. Evidence increasingly points to an infectious etiology,[32] but debate continues on
whether the cause is a conventional antigenic substance or a superantigen.[33]Children's
Hospital Boston reports that "[s]ome studies have found associations between the
occurrence of Kawasaki disease and recent exposure to carpet cleaning or residence near a
body 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 codes
an enzyme that negatively regulates T-cell activation.[34] An additional factor that suggests
genetic susceptibility is the fact that regardless of where they are living, Japanese children
are more likely than other children to contract the disease. [28] The HLA-B51 serotype has
been 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 at

least 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, including

peripheralerythema, peripheral edema,
periungual desquamation, and generalized
desquamation

Polymorphous rash, primarily truncal

Cervical lymphadenopathy >1.5 cm in diameter

Disease cannot be explained by some other known

disease process

†A diagnosis of Kawasaki disease can be made if

fever and only 3 changes are present in conjunction
with coronary artery disease documented by two-
dimensional echocardiography or coronary
angiography.

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
diagnosis, especially early in the course of the illness, and frequently children are not
diagnosed until they have seen several health care providers. Many other serious illnesses
can cause similar symptoms, and must be considered in the differential diagnosis,
including scarlet fever, toxic shock syndrome, juvenile idiopathic arthritis, and childhood
mercury 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 exhibit
all of the above criteria. In fact, many experts now recommend treating for Kawasaki
disease even if only three days of fever have passed and at least three diagnostic criteria
are 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 aneurysms
in 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 and

eventually 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 remains
the gold standard for their detection, but is rarely used today unless coronary artery
aneurysms have already been detected by echocardiography.

[edit]Treatment

Children with Kawasaki disease should be hospitalized and cared for by a physician who has
experience with this disease. When in an academic medical center, care is often shared
between pediatriccardiology and pediatric infectious disease specialists (although no
specific infectious agent has been identified yet).[28] It is imperative that treatment be
started 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 is
administered in high doses with marked improvement usually noted within 24 hours. If the
fever does not respond, an additional dose may have to be considered. In rare cases, a third
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 (though
questioned by some)[40] but salicylates alone are not as effective as IVIG. Aspirin therapy is
started at high doses until the fever subsides, and then is continued at a low dose when the
patient 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 not
recommended for children due to its association with Reye's syndrome. Because children
with Kawasaki disease will be taking aspirin for up to several months, vaccination
against varicella and influenza is required, as these infections are most likely to cause
Reye's syndrome.[41]
Corticosteroids have also been used,[42] especially when other treatments fail or symptoms
recur, but in a randomized controlled trial, the addition of corticosteroid to immune globulin
and 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 include
the 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 risk
of coronary artery aneurysms greatly reduced. Untreated, the acute symptoms of Kawasaki
disease are self-limited (i.e. the patient will recover eventually), but the risk of coronary
artery involvement is much greater. Overall, about 2% of patients die from complications of
coronary vasculitis. Patients who have had Kawasaki disease should have
an echocardiogram initially every few weeks, and then every one or two years to screen for
progression of cardiac involvement.
It is also not uncommon that a relapse of symptoms may occur soon after initial treatment
with 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 for
Kawasaki 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 clinical
lexicon in recent years. They are being used as synonyms for asthma. The terms are widely
used in case presentations involving outpatients and inpatients, and even patients in
intensive care units. They are in particular commonly used in the pediatric setting. The
problem is that "reactive airways" and "reactive airways disease" are highly nonspecific
terms 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, sputum
production, 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. Most
often, physicians who use the terms do not have pulmonary function test results for the
patient. Certainly, it is very rare that patients have had measurement of airway reactivity to
methacholine, histamine, or hypertonic saline. Therefore, armed only with symptoms
referable to the airway, or with a history of inhaler use, the doctor will present on rounds or
write in the chart, in letters, or in discharge summaries that the patient has "reactive airways
disease." Unfortunately, this diagnosis often goes unchallenged. In fact, increasingly the
term is beingcommonly used among specialists in pulmonary medicine.

The term "reactive airways disease" needs to be distinguished from reactive airways
dysfunction syndrome (RADS) and from airway hyperreactivity two terms that have value
and meaning in pulmonary medicine. RADS is a specific term coined by Brooks and
coworkers (1) in 1985 to describe an asthma-like illness developing after a single exposure to
high levels of an irritating vapor, fume, or smoke. Patients with RADS have methacholine
airway hyperreactivity, but other pulmonary function tests may or may not be
abnormal. Symptoms and airway hyperreactivity can persist for years afterthe incriminating
exposure. RADS differs from occupational asthma in that it typically occurs after a single
exposure without a preceding period of sensitization. It should be noted that not all experts
agree that RADS is a real clinical syndrome (2), arguing that the entity is based on case
reports that lack control groups and that usually lack preexposure pulmonary function
assessment. However, the weight of current scientific evidence supports RADS as a distinct
clinical entity, and the disorder is currently recognized as distinct by the American Thoracic
Society and the American College of Chest Physicians (3).

Airway hyperreactivity is also a specific term that means that the airways are hyperreactive
to a variety of stimuli includingmethacholine, histamine, hypertonic saline, distilled water,
exercise, or eucapnic hyperventilation (4). Hyperreactivity in this context means a
bronchoconstrictor response at "doses" that normally have no bronchoconstrictor effect.
Airway hyerreactivity actually encompasses both airway sensitivity (the dose of agonist at
which the FEV1 begins to fall) and airway hyperresponsiveness (the slope of the dose-
response curve thereafter). Airway hyperreactivity is a characteristicof asthma and to a
lesser extent of chronic obstructive pulmonary disease (COPD) (5), but has also been
described in patients with allergic rhinitis (6), but no asthma, in cystic fibrosis (7), and even
in irritable bowel disease (8). Thus, although airway hyperreactivity is a highly specific term
with definite meaning, it is not a disease diagnosis; rather it represents a physiological
abnormality of the airway. It is, however, an important component of the diagnostic criteria
forasthma.

The use of the term "reactive airways disease" in part reflects the difficulty with establishing
a diagnosis of asthma in some situations. In the pediatric setting, especially in very young
children, the diagnosis of asthma may be problematic becausethe history is difficult to
obtain, because good quality pulmonary function tests cannot be obtained, or because
asthma 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 ranging
from asthma, to wheezy bronchitis, to viral bronchiolitis, or even to pneumonia. In adult
medicine, we suspect that the term is popular because of instances in which physicians
obtain 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 they
represent an annoyance to purists of terminology. The problem is that using the terms may
provide physicians with a false sense of diagnosis security. Ascribing a label of reactive
airways to a patient may be harmful in this context, because it may prevent work-up of the
cause of the symptom complex that led to the diagnosis of reactive airways disease in the
first place. These patients may actually have asthma, chronic bronchitis, emphysema, or
even pneumonia. Treatment usually prescribed for these specific diseases may or may not
be prescribed if the diagnosis is "reactive airways disease." Overtreatment may also be a
side 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 treatments
benefit the patient.

Finally, the terms "reactive airways" and "reactive airways disease" are now making their
way from the clinical lexicon tothe clinical literature. Two recent publications have used
the term "reactive airway disease" (9, 10). In one instance reactive airway disease was used
as a summary term to describe patients with asthma and/or COPD; in the other it was used
synonymously with airway hyperreactivity (10). We find this trend troubling because many
patients considered to have "reactive airways disease" do not have asthma, and the vast
majority of patients with reactive airways have never had their airway reactivity measured.
We believe it essential to preserve the integrity of asthma and airway hyperactivityas
diagnostic terms in the clinical literature. In fact, in the context of clinical research, we
believe the use of the terms"reactive airways" and "reactive airways disease" will
complicate research on asthma, especially for clinical epidemiologists who are investigating
the current worldwide epidemic of asthma.

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

Asthma, also known as "hyperactive airways," is classified as a reversible obstructive

respiratory disorder. (5) In this disease, smooth muscle dysfunction and airway inflammation
combine to result in airflow obstruction and airway hyper-responsiveness - leading to a
narrowing of the airways. Until recently, asthma treatment has focused on the first of these
two mechanisms, smooth muscle dysfunction, because it is the one responsible for the most
obvious 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). For
what reason would the body desire to cut off its own air supply? Nonetheless, these tiny
muscles exist, and an asthmatic is well aware of their presence.
During normal respiration these bands of muscle are relaxed and air is allowed to move
freely. However, in people with asthma these muscles may spasm or tighten, clamping down
on the bronchial tubes. This constriction of airflow into and out of the lungs is where an
asthmatic gets his characteristic wheeze.
Airflow obstruction in asthma may result from any one of a number of events, with
bronchoconstriction being just one of the players. Airway edema, mucus plug formation, and
airway remodeling can also all cause airflow obstruction.(7) In fact, within the last ten years
or so it has become apparent that involuntary constriction of the smooth muscle lining the
bronchial 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 fundamental
role 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 to
prevent further exacerbation.[113] monteleukast ( singulair) is used as an adjuctive in the
treatment of persistant type asthma and allows the tapering of high dose inhaled steroids. it
is also effective in mild persistant type asthma but less evidence suggest use in intermittent
type asthma.
Fast acting

 Short-acting, selective beta2-adrenoceptor agonists, such

as salbutamol (albuterol USAN), levalbuterol, terbutaline and bitolterol.[citation needed]

Tremors, the major side effect, have been greatly reduced by inhaled delivery, which
allows the drug to target the lungs specifically; oral and injected medications are
delivered 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 more
anti-inflammatory effects on bronchial smooth muscle than its racemic counterpart
albuterol. The question becomes does this justify its 5-10 fold higher cost. Some
hospitals start a patient on levalbuterol until symptoms wane and then switch to
albuterol. Patients must be cautioned against using these medicines too frequently, as
with such use their efficiency may decline, producing desensitization resulting in an
exacerbation of symptoms which may lead to refractory asthma and death.[citation needed]
 Older, less selective adrenergic agonists, such as
inhaled epinephrine and ephedrine tablets, have also been used; the brand Primatene
Mist, for example. Cardiac side effects occur with these agents at either similar or lesser
rates to albuterol.[114] [115] When used solely as a relief medication, inhaled epinephrine
has 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 by
injection. 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 heart
disease; however, they take up to an hour to achieve their full effect and are not as
powerful as the β2-adrenoreceptor agonists.[citation needed]

Long term control

 Inhaled glucocorticoids are mainly considered as preventive medications while oral

glucocorticoids are often used to supplement treatment of emergent moderate to severe
attacks.[116] They should be used twice daily in children with mild to moderate persistent
asthma.[117][non-primary source needed] A randomized controlled trial has demonstrated the benefit
of 250 microg beclomethasone when taken as an as-needed combination inhaler with
100 microg of albuterol.[118][non-primary source needed]
 Long-acting β2-agonists (LABD) are similar in structure to short-acting selective beta 2-
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 replace
the need for routine preventers, and their slow onset means the short-acting dilators are
still be required. In November 2005, the American FDA released a health advisory
alerting the public to findings that show the use of long-acting β2-agonists could lead to a
worsening 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 these
medications in children. Discussion is ongoing about their use in adults.[120] A recent
meta-analysis of long-acting beta-agonists indicate a danger in asthma with an 2—4 fold
increased risk for asthma hospitalizations and asthma deaths compared with placebo.[121]

Medications are typically provided as metered-dose inhalers (MDIs) in combination with

an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the
medication with air, making it easier to receive a full dose of the drug. A nebulizer may also
be used. There is no clear evidence, however, that they are more effective than inhalers
used with a spacer.