08/06/13

Upper Respiratory Tract Infection

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Upper Respiratory Tract Infection

Author: Anne Meneghetti, MD; Chief Editor: Zab Mosenifar, MD more... Updated: Oct 15, 2012

Practice Essentials
The VIDARIS trial, a randomized, placebo-controlled study from New Zealand that enrolled 322 adults older than age 18 years who were in good health, found that adding vitamin D supplements to the diet neither prevented upper respiratory tract infections (URIs) nor hastened recovery from them.[1, 2] Before this study, it had been unclear whether vitamin D supplementation played a role in preventing or mitigating URIs. Several previous observational studies showed an inverse association between 25-hydroxyvitamin D levels and the presence of URIs, and basic research suggested that vitamin D could help clear bacteria, build up epithelial barriers to infection, and enhance antigen-presenting cells. However, there had been no definitive trial to determine whether vitamin D therapy actually reduces URI rates in adults. Participants in the trial were randomly assigned to 1 of the following 2 groups: Active intervention group An initial oral vitamin D3 dose of 200,000 IU, followed by a second dose of 200,000 IU the following month and then by monthly doses of 100,000 IU for 16 months Placebo group Matched placebo on the same dosing schedule Researchers determined the number, duration, and severity of URI episodes, as well as their effect on the patients productivity at work (quantified in terms of days missed because of URIs). Results were as follows: No significant difference between treatment and placebo groups in total number of URIs (593 events in the intervention group and 611 in the placebo group) No significant difference in number of URIs per person (mean, 3.7 per person in the intervention group and 3.8 per person in the placebo group) No significant difference in symptom duration per URI episode (mean, 12 days in each group) No significant difference in severity of URIs No significant difference in number of days missed from work because of URIs (mean, 0.76 days in each group) The findings did not change significantly when the analysis was repeated by season and by baseline 25-OHD (25hydroxyvitamin D) levels. Although the authors did not find a benefit of vitamin D supplementation in their study, they note that other populations (eg, a population with a higher prevalence of vitamin D deficiency) might benefit from vitamin D supplementation. Although at present, clear evidence of the benefit of vitamin D exists only for bone health, investigation into ways in which vitamin D intake might be related to improving immune function and preventing infection remains an important area for future research.
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For further information, see the following: Presentation Workup Treatment See also the image below:

Seasonal variation of selected upper respiratory tract infection pathogens. PIV is parainfluenza virus, RSV is respiratory syncytial virus, MPV is metapneumovirus, and Group A Strept is group A streptococcal disease.

Background
URI represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold--typically a mild, self-limited, catarrhal syndrome of the nasopharynx--to life-threatening illnesses such as epiglottitis. Viruses account for most URIs. Bacterial primary infection or superinfection may require targeted therapy. The upper respiratory tract includes the sinuses, nasal passages, pharynx, and larynx, which serve as gateways to the trachea, bronchi, and pulmonary alveolar spaces. Rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis, and tracheitis are specific manifestations of URIs. Further information can be found in the Medscape Reference articles Emergent Management of Acute Otitis Media, Bronchiolitis, and Bronchitis, and in articles about specific infectious agents. Common URI terms are defined as follows: Rhinitis - Inflammation of the nasal mucosa Rhinosinusitis or sinusitis - Inflammation of the nares and paranasal sinuses, including frontal, ethmoid, maxillary, and sphenoid Nasopharyngitis (rhinopharyngitis or the common cold) - Inflammation of the nares, pharynx, hypopharynx, uvula, and tonsils Pharyngitis - Inflammation of the pharynx, hypopharynx, uvula, and tonsils Epiglottitis (supraglottitis) - Inflammation of the superior portion of the larynx and supraglottic area Laryngitis - Inflammation of the larynx Laryngotracheitis - Inflammation of the larynx, trachea, and subglottic area Tracheitis - Inflammation of the trachea and subglottic area

Pathophysiology
URIs involve direct invasion of the mucosa lining the upper airway. Person-to-person spread of viruses accounts for most URIs. Patients with bacterial infections may present in similar fashion, or they may present with a superinfection of a viral URI. Inoculation by bacteria or viruses begins when secretions are transferred by touching a hand exposed to pathogens to the nose or mouth or by directly inhaling respiratory droplets from an infected person who is coughing or sneezing. After inoculation, viruses and bacteria encounter several barriers, including physical, mechanical, humoral, and cellular immune defenses. Hair lining the nose filters and traps some pathogens. Mucus coats much of the upper respiratory tract, trapping potential invaders. The angle resulting from the junction of the posterior nose to the pharynx causes large particles to impinge on the back of the throat. Ciliated cells lower in the respiratory tract trap and transport pathogens up to the pharynx; from there they are swallowed into the stomach.
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Adenoids and tonsils contain immune cells that respond to pathogens. Humoral immunity (immunoglobulin A) and cellular immunity act to reduce infections throughout the entire respiratory tract. Resident and recruited macrophages, monocytes, neutrophils, and eosinophils coordinate to engulf and destroy invaders. A host of inflammatory cytokines mediates the immune response to invading pathogens. Normal nasopharyngeal flora, including various staphylococcal and streptococcal species, help defend against potential pathogens. Patients with suboptimal humoral and phagocytic immune function are at increased risk for contracting a URI, and they are at increased risk for a severe or prolonged course of disease. Viral agents include a vast number of serotypes, which undergo frequent changes in antigenicity, posing challenges to immune defense. Pathogens resist destruction by a variety of mechanisms, including the production of toxins, proteases, and bacterial adherence factors, as well as the formation of capsules that resist phagocytosis. Incubation times before the appearance of symptoms vary among pathogens. Rhinoviruses and group A streptococci may incubate for 1-5 days, influenza and parainfluenza may incubate for 1-4 days, and respiratory syncytial virus (RSV) may incubate for a week. Pertussis typically incubates for 7-10 days or even as long as 21 days before causing symptoms. Diphtheria incubates for 1-10 days. The incubation period of Epstein-Barr virus (EBV) is 4-6 weeks. Most symptoms of URIs, including local swelling, erythema, edema, secretions, and fever, result from the inflammatory response of the immune system to invading pathogens and from toxins produced by pathogens. An initial nasopharyngeal infection may spread to adjacent structures, resulting in sinusitis, otitis media, epiglottitis, laryngitis, tracheobronchitis, and pneumonia. Inflammatory narrowing at the level of the epiglottis and larynx may result in a dangerous compromise of airflow, especially in children, in whom a small reduction in the luminal diameter of the subglottic larynx and trachea may be critical. Beyond childhood, laryngotracheal inflammation may also pose serious threats to individuals with congenital or acquired subglottic stenosis.

Epidemiology
Frequency
United States URIs are the most common infectious illness in the general population. URIs are the leading reasons for people missing work or school, and they represent the leading acute diagnosis in the office setting.[3] Nasopharyngitis The incidence of the common cold varies by age. Rates are highest in children younger than 5 years. Children who attend school or daycare are a large reservoir for URIs, and they transfer infection to those who care for them. Children have about 3-8 viral respiratory illnesses per year. Adolescents and adults have approximately 2-4 colds a year, and people older than 60 years have fewer than 1 cold per year. Pharyngitis Acute pharyngitis accounts for 1% of all ambulatory office visits.[3] The incidence of viral and bacterial pharyngitis peaks in children aged 4-7 years. Rhinosinusitis Sinusitis is common in persons with viral URIs. Transient changes in the paranasal sinuses are noted on CT scans in more than 80% of patients with uncomplicated viral URIs.[4] However, bacterial rhinosinusitis occurs as a complication in only about 2% of persons with viral URIs.[5] Epiglottitis Epiglottitis occurs at a rate of 6-14 cases per 100,000 children, based on estimates from other countries.[6] This condition typically occurs in children aged 2-7 years and has a peak incidence in those aged 3 years.[7] Epiglottitis is estimated to occur at annual incidence of 9.7 cases per million adults.[8] The occurrence of epiglottitis has decreased dramatically in the United States since the introduction of the Haemophilus influenzae type B (Hib) vaccine. Laryngitis and laryngotracheitis
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Croup, or laryngotracheobronchitis, may affect people of any age, but usually occurs in children aged 6 months to 6 years. The peak incidence is in the second year of life.[7] Thereafter, the enlarging caliber of the airway reduces the severity of the manifestations of subglottic inflammation. Vaccination has dramatically reduced rates of pertussis, including whooping cough. However, the incidence of whooping cough cases in the United States has increased in recent years, reaching 5.3 cases per 100,000 population in 2006.[9] Adolescents and infants younger than 5 months account for many of these cases. In 2004, adults aged 19-64 years accounted for 7,008 (27%) of 25,827 reported cases of pertussis in the United States. Challenges in laboratory diagnosis and overreliance on polymerase chain reaction (PCR) tests have resulted in reports of respiratory illness outbreaks mistakenly attributed to pertussis.[10] Frequency of selected pathogens Group A streptococcal bacteria cause approximately 5-15% of all pharyngitis infections, accounting for several million cases of streptococcal pharyngitis each year. This infection is rarely diagnosed in children younger than 2 years. Approximately 5-20% of Americans have the flu during each flu season.[11] Early presentations include symptoms of URI. EBV infection affects as many as 95% of American adults by age 35-40 years. Childhood EBV infection is indistinguishable from other transient childhood infections. Approximately 35-50% of adolescents and young adults who contract EBV infection have mononucleosis.[12] After the advent of the diphtheria vaccine, case rates dramatically decreased in the United States. Since 1980, the prevalence has been approximately 0.001 case per 100,000 population.[13] Diphtheria remains endemic in developing countries. Sporadic cases have recently affected adults. Seasonality Although URIs may occur year round, in the United States, most colds occur during fall and winter. Beginning in late August or early September, rates of colds increase over several weeks and remain elevated until March or April.[14] Epidemics and miniepidemics are most common during cold months, with a peak incidence in late winter to early spring. Cold weather means more time spent indoors (eg, at work, home, school) and close exposure to others who may be infected. Humidity may also affect the prevalence of colds, because most viral URI agents thrive in the low humidity characteristic of winter months. Low indoor air moisture may increase friability of the nasal mucosa, increasing a person's susceptibility to infection. Laryngotracheobronchitis, or croup, occurs in fall and winter. Seasonality does not affect rates of epiglottitis. The figure below illustrates the peak incidences of various agents by season. Rhinoviruses, which account for a substantial percentage of URIs, are most active in spring, summer, and early autumn. Coronaviral URIs manifest primarily in the winter and early spring. Enteroviral URIs are most noticeable in summer and early fall, when other URI pathogens are at a nadir. Adenoviral respiratory infections are most common in the late winter, spring, and early summer, yet they can occur throughout the year.

Seasonal variation of selected upper respiratory tract infection pathogens. PIV is parainfluenza virus, RSV is respiratory syncytial virus, MPV is metapneumovirus, and Group A Strept is group A streptococcal disease.

Seasonal influenza typically lasts from November until March. In 2009, H1N1 influenza activity was present throughout summer and autumn, overlapping with seasonal influenza. Some parainfluenza viruses (PIVs) have a biennial pattern. Human PIV type 1, the leading cause of croup in children, currently causes autumnal outbreaks in the United States during odd-numbered years. Human PIV type 2 may cause annual or biennial fall outbreaks. Peak activity for human PIV type 3 is during the spring and early summer months; however, the virus may be isolated throughout the year.[13] Human metapneumovirus (hMPV) infection may also occur year round, peaking
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between December and February.

Mortality/Morbidity
URIs cause people to spend time away from their usual daily activities. Alone, URIs rarely cause permanent sequelae or death, although URIs may serve as a gateway to infection of adjacent structures, resulting in otitis media, bronchitis, bronchiolitis, pneumonia, sepsis, meningitis, intracranial abscess, and other infections. Serious complications may result in clinically significant morbidity and rare deaths. Common cold This is the leading cause of acute morbidity and missed days from school or work. The common cold is also the leading acute cause of office visits to a physician in the United States. Untreated group A streptococcal pharyngitis This infection can result in acute rheumatic fever (ARF), acute glomerulonephritis, peritonsillar abscess, and toxic shock syndrome. Mortality from group A streptococcal pharyngitis is rare, but serious morbidity or death may result from one of its complications. Pharyngitis without complications rarely poses significant risk for morbidity. However, retropharyngeal, intraorbital, or intracranial abscesses may cause serious sequelae. Sinusitis The condition itself is rarely life threatening, but sinusitis can lead to serious complications if the infection extends into surrounding deep tissue. Examples include orbital cellulitis, subperiosteal abscess, orbital abscess, frontal and maxillary osteomyelitis, subdural abscess, meningitis, and brain abscess. Epiglottitis This infection poses a risk of death due to sudden airway obstruction and other complications, including septic arthritis, meningitis, empyema, and mediastinitis. In adults, epiglottitis has a fatality rate of approximately 1%. Selected pathogens Approximately 3-6% of cases of Hib disease are fatal. Each year, more than 200,000 people are hospitalized for influenza and approximately 36,000 people die from seasonal influenza and its complications.[11] CDC estimates the overall death rate associated with 2009 H1N1 influenza was 0.97 per 100,000 persons across all age groups.[15] Complications from whooping cough, or pertussis, reported from 2001-2003 included 56 pertussis-related deaths. Fifty-one (91%) of these deaths were among infants younger than 6 months, and 42 (75%) were among infants younger than 2 months.[16] Approximately 5-10% of patients with diphtheria die. Fatality rates up to 20% are reported in patients younger than 5 years or older than 40 years.[16]

Race
No notable racial difference is observed with URIs. However, Alaskan Natives have rates of Hib disease higher than those of other groups.[17]

Sex
Rhinitis: Hormonal changes during the middle of the menstrual cycle and during pregnancy may produce hyperemia of the nasal and sinus mucosa and increase nasal secretions. URI may be superimposed over these baseline changes and may increase the intensity of symptoms in some women. Nasopharyngitis: The common cold occurs frequently in women, especially those aged 20-30 years.[14] This frequency may represent increased exposure to small children, who represent a large reservoir for URIs. However, hormonal effects on the nasal mucosa may also play a role. Epiglottitis: A male predominance is reported, with a male-to-female ratio of approximately 3:2.
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Laryngotracheobronchitis, or croup, is more common in boys than in girls, with male-to-female ratio of approximately 3:2.[7]

Age
Nasopharyngitis: The incidence of the common cold varies by age. Rates are highest in children younger than 5 years. Children have approximately 3-8 viral respiratory illnesses per year. Adolescents and adults have approximately 2-4 colds a year, and people older than 60 years have fewer than 1 cold per year. Pharyngitis: The incidence of viral and bacterial pharyngitis peaks in children aged 4-7 years. Epiglottitis: This typically occurs in children aged 2-7 years and has a peak incidence in those aged 3 years.[7] Laryngitis and laryngotracheitis: Croup, or laryngotracheobronchitis, may affect people of any age, but it usually occurs in children aged 6 months to 6 years. The peak incidence is in the second year of life.[7]

Contributor Information and Disclosures

Author Anne Meneghetti, MD Assistant Professor of Medicine, Tufts University School of Medicine; Medical Broadcaster, Life, Love and Health, RealForMe.com Anne Meneghetti, MD is a member of the following medical societies: National Ayurvedic Medical Association Disclosure: Nothing to disclose. Chief Editor Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society Disclosure: Nothing to disclose. Additional Contributors Gregory William Rutecki, MD Professor of Medicine, Fellow of The Center for Bioethics and Human Dignity, University of South Alabama College of Medicine Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, and Society of General Internal Medicine Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment

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