Cough in children
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:
Synonyms and keywords: Cough in kids
Overview
Historical Perspective
- The word Cough was first derived from the middle English Coughen or old English Cohhian which was primarily composed of the middle Dutch Kochen and the high middle German Kuchen, in early 14th century.
Classification
- Cough in children may be classified or defined according to the duration of presenting complaints, quality and sound, causes of cough into several groups.[1]:
- 1 Duration of Presenting complaints: According to the duration of cough, it can be sub classified into three categories.
- Acute: Cough persists for less than three weeks.
- Subacute: Cough persists for three to eight weeks.
- Chronic: Cough persists for more than eight weeks.
- 2. Quality and sounds: According to the quality and sound cough can be sub classified in to following categories-
- Dry or Hacking or Nonproductive.
- Wet or productive cough.
- Staccato or short repetitive cough.
- Whooping or paroxysmal violent or spasmodic cough.
- Barking cough: Brassy barking or Honking barking.
- Phlegmy cough.
- Burning cough.
- 3. Causes of Cough: Based on causes cough is subdivided into following three sub groups-
- Normal or expected cough.
- Specific cough.
- Non-specific cough.
- 4. Anatomic classification on causes of cough: Cough can be produced from different anatomical locations. for example-
- Nose and Paranasal sinuses.
- Pharynx.
- Larynx.
- Trachea and Bronchi.
- Pulmonary parenchyma.
- Pleura.
- Mediastinum.
- Heart and blood vessels.
- External ear and Tympanic membrane.
- Esophagus.
- 5. Grades of cough: Cough can be graded into four main sub categories-[2]
- Eutussia or Normal.
- Hypertussia or Sensitized.
- Hypotussia or Desensitized.
- Dystussia or Pathological.
- Atussia or Absent.
Cough in children can also be classified under infectious (Bacterial, Viral, fungal, Parasitic) or non-infectous categories broadly.
Pathophysiology
- Cough is natural innate primitive reflex that helps in mucocilliary clearance of foreign particles and secretions from respiratory tracts. It is also a defensive mechanism protecting respiratory airways from aspiration of pathogens, particulates and secretions. A complex arc comprised of neuro-respiratory pathways helps in initiating the cough reflex.[3]
Mechanical and chemical stimulation of cough receptors (Rapidly adapting receptors, slowly adapting receptors or C-fibers) in Respiratory airways | |||||||||||||||||||
Afferent pathways: Sensory nerve fibers via Vagus Nerve from ciliated columnar epithelium of upper airways, cardiac and esophageal branches from diaphragm send impulse to central cough center | |||||||||||||||||||
Central cough center in upper brain stem medulla and pons send impulse of sequence of phases (Inspiratory, Compressive, Expiratory) for constituting cough | |||||||||||||||||||
Efferent pathways: The nucleus retroambigualis sends impulse via phrenic and spinal motor nerves to diaphragm and abdominal and respiratory muscles, the nucleus ambiguous sends impulse to larynx by laryngeal branches of vagus nerve | |||||||||||||||||||
- On gross pathology, Bloody, Serous , Mucoid, Rusty, Pink frothy, and Purulent are characteristic findings of sputum produced by coughing.
- On microscopic histopathological analysis, Pathogens, RBCs, Leukocytes, epithelial celss are characteristic findings of Sputum produced by coughing.
Causes
Causes of cough in children according to duration[4][5][6]:
Cough | |||||||||||||||||||||||||||||||||||
Acute(<3 weeks) •Common Cold •Allergic Rhinitis •Bronchitis •Bronchiolitis •Asthma •Whooping Cough •Influenza •Croup or Tracheolaryngobronchitis •Pneumonia •Irritation by smoking •Foreign Body •GERD | Subacute(3-8 weeks) •Whooping Cough or Pertussis •Post infectious Cough •Bacterial Sinusitis •Asthma | Chronic(>8 weeks) •Upper Airway Cough Syndrome •Asthma •Bronchiectasis in Cystic fibrosis and Kartagener Syndrome •Chronic sinusitis •Malacia •Foreign Body •Nonasthmatic eosinophilic bronchitis •Respiratory environmental toxins | |||||||||||||||||||||||||||||||||
According to quality and sound of cough in children, the causes can be classified according to following chart.
Dry or Hacking or Nonproductive | Sinusitis, Tonsillitis, Pharyngitis, Allergic Rhinitis, GERD, Asthma, Environmental exposure to irritants(pollen, dust, mites, smokes), Post infectious cough. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Wet or productive cough | Cystic fibrosis, Bronchiectasis, Bronchiolitis, Tuberculosis, Rhinitis, Postnasal drip, Pneumonia, Emphysema, Acute bronchitis, Asthma | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Causes of Cough based on quality and sound | Staccato or short repetitive cough | Chlamydia pneumonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Whooping or paroxysmal violent or spasmodic cough | Pertussis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Barking cough | •Brassy barking: Croup, Tracheomalacia, Laryngitis, Tracheitis •Honking barking: Psychogenic cough , Tourette syndrome (habit cough) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Phlegmy cough | Viral infection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Burning cough | Bacterial Bronchitis, Irritants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Based on anatomical location the causes of cough in children can be demonstrated into following chart-
Differentiating Cough from other Diseases
For the differential diagnosis of productive cough, click here.
For the differential diagnosis of acute cough, click here.
For the differential diagnosis of chronic cough, click here.
For the differential diagnosis of cough and hemoptysis, click here.
For the differential diagnosis of cough and weight loss, click here.
For the differential diagnosis of cough and fever, click here.
For the differential diagnosis of cough and wheeze, click here.
For the differential diagnosis of cough, fever, and hemoptysis, click here.
For the differential diagnosis of cough, fever, and weight loss, click here.
For the differential diagnosis of cough, hemoptysis, and weight loss, click here.
Organ system | Diseases | Clinical manifestations | Diagnosis | Other features | |||||||||||
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Symptoms | Physical exam | ||||||||||||||
Onset | Duration | Productive cough | Hemoptysis | Weight lost | Fever | Dyspnea | Ascultation | Lab findings | Imaging | PFT | Gold standard | ||||
Respiratory | Upper airway diseases | Epiglottitis[7][8] | Abrupt or acute |
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− | − | − | + | + |
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Croup[9] | Acute |
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+ | − | − | + | + |
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Pertussis[10][11] | Acute |
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+ Whooping sound | − | + | + | + |
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Laryngopharyngeal reflux[12][13] | Chronic |
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+ | − | − | − | + |
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Common Cold[14] | Acute |
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+ | − | − | + | − |
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Seasonal Influenza [15] | Acute |
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− | − | − | + | + |
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Rhinosinusitis[16][17] | Acute, subacute, chronic, recurrent | + | − | − | + | + |
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Organ system | Diseases | Clinical manifestations | Diagnosis | Other features | |||||||||||
Symptoms | Physical exam | ||||||||||||||
Onset | Duration | Productive cough | Hemoptysis | Weight lost | Fever | Dyspnea | Ascultation | Lab findings | Imaging | PFT | Gold standard | ||||
Respiratory | Lower airway | Asthma[18] | Chronic |
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+ Clear mucoid or yellow sputum | − | − | − | + |
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Acute Bronchitis[19] | Acute |
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+ | − | − | +/− | + |
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Chronic Bronchitis[20][21] | Chronic |
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+ Clear sputum | − | − | + | + |
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Non−asthmatic eosinophilic bronchitis[22][23] | Chronic |
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+ Eosinophilic sputum | − | − | − | + |
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Bronchiectasis[24] | Chronic |
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+ Mucopurulent sputum | + | − | − | + |
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Emphysema [25] | Chronic |
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+ Mucoid or purulent sputum | − | − | + | + |
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Foreing body aspiration[26][27][28] | Acute |
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+ | + | − | + | + |
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Bronchiolitis[29][30] | Acute |
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+ | − | − | + | + |
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Organ system | Diseases | Clinical manifestations | Diagnosis | Other features | |||||||||||
Symptoms | Physical exam | ||||||||||||||
Onset | Duration | Productive cough | Hemoptysis | Weight lost | Fever | Dyspnea | Ascultation | Lab findings | Imaging | PFT | Gold standard | ||||
Respiratory | Parenchyma | Pneumonia[31][32] | Acute |
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+ Mucopurulent sputum | − | − | + | + |
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Pneumoconioses[33][34] | Acute, Chronic |
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− | − | + | + | + |
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Lung cancer[35][36] | Chronic |
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+ | + | + | +/− | + | The following investigations may be helpful: |
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Interstitial lung disease[37][38] | Chronic |
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− | + | + | − | + |
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The following investigations may be helpful: |
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Tuberculosis (TB)[39][40] | Chronic |
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+ | + | + | + | + |
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Cystic fibrosis (CF)[41][42] | Chronic |
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+ | − | + | +/− | + |
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Organ system | Diseases | Clinical manifestations | Diagnosis | Other features | |||||||||||
Symptoms | Physical exam | ||||||||||||||
Onset | Duration | Productive cough | Hemoptysis | Weight lost | Fever | Dyspnea | Ascultation | Lab findings | Imaging | PFT | Gold standard | ||||
Cardiac | Cardiogenic pulmonary edema[43][44] | Acute |
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+ Pink frothy, liquid | − | + | − | + |
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The following investigations may be helpful: |
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Mitral Stenosis[45][46] | Chronic |
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+ Pink frothy | + | − | − | + |
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Pulmonary hypertension[47][48] | Chronic |
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− | + | + | − | + | The following investigations may be helpful: |
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Gastrointestinal | Gastroesophageal reflux[49][50] | Chronic |
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+ | − | + | − | + |
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−− | ||
Organ system | Diseases | Clinical manifestations | Diagnosis | Other features | |||||||||||
Symptoms | Physical exam | ||||||||||||||
Onset | Duration | Productive cough | Hemoptysis | Weight lost | Fever | Dyspnea | Ascultation | Lab findings | Imaging | PFT | Gold standard | ||||
Autoimmune | Goodpasture syndrome[51][52] | Chronic |
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− | + | − | − | + | The following investigations may be helpful:
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Wegener's disease (GPA) [53][54] | Chronic |
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+ | + | + | + | + | The following investigations may be helpful: |
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Sarcoidosis[55][56] | Chronic |
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− | − | + | + | + |
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The following investigations may be helpful: |
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Microscopic polyangitis (MPA)[57] | Chronic |
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+ | + | + | + | + | The following investigations may be helpful:
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Churg−Strauss[58][59] | Chronic |
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+ | + | + | + | + |
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Medication | ACE inhibitors[60][61] | Acute (depend on the medication) |
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− | − | − | − | + |
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Epidemiology and Demographics
- Cough is one of the most common symptoms of children in outpatient department.
- Ninety percent of acute cough in children is resolved within three weeks. The prevalence of Chronic Cough in children is approximately 5% to 10% in USA according to American Academy of Pediatrics.
Age
- Cough is more commonly observed among children under 5 years of age.[62]
Gender
- Boys are more commonly affected with cough than girls.[63]
Race
- There are racial predilection for certain causes of Cough in children. Asthma is predominant in Blacks and American Indians or Alaska native while Cystic fibrosis, Wegener's granulomatosis are more frequently affecting Caucasians according to American Lung Association.
Risk Factors
- Common risk factors in the development of Cough in children are-
- Preterm Birth and delivery by caesarian section.
- Respiratory Distress Syndrome.
- Congenital Heart Disease.
- Age less than 1 year.
- Maternal Influenza vaccination.
- Malnutrition.
- Secondary exposure to tobacco smoke.
- Air pollutants, Mold, Inadequate ventilation.
- Immunodeficiencies.
- Daycare attendance.
- History of Atopy.
- Household pets.
- Low socioeconomic status.
Natural History, Complications and Prognosis
- The majority of patients with [disease name] remain asymptomatic for [duration/years].
- Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
- If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
- Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
- Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
Diagnosis
Diagnostic Criteria
- The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
- [criterion 1]
- [criterion 2]
- [criterion 3]
- [criterion 4]
Symptoms
- [Disease name] is usually asymptomatic.
- Symptoms of [disease name] may include the following:
- [symptom 1]
- [symptom 2]
- [symptom 3]
- [symptom 4]
- [symptom 5]
- [symptom 6]
Physical Examination
- Patients with [disease name] usually appear [general appearance].
- Physical examination may be remarkable for:
- [finding 1]
- [finding 2]
- [finding 3]
- [finding 4]
- [finding 5]
- [finding 6]
Laboratory Findings
- There are no specific laboratory findings associated with [disease name].
- A [positive/negative] [test name] is diagnostic of [disease name].
- An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
- Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
Electrocardiogram
There are no ECG findings associated with [disease name].
OR
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
X-ray
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
OR
Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
- [Disease name] may also be diagnosed using [diagnostic study name].
- Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
- There is no treatment for [disease name]; the mainstay of therapy is supportive care.
- The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
- [Medical therapy 1] acts by [mechanism of action 1].
- Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
Surgery
- Surgery is the mainstay of therapy for [disease name].
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
- [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
Prevention
- There are no primary preventive measures available for [disease name].
- Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
- Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
References
- ↑ Alsubaie H, Al-Shamrani A, Alharbi AS, Alhaider S (March 2015). "Clinical practice guidelines: Approach to cough in children: The official statement endorsed by the Saudi Pediatric Pulmonology Association (SPPA)". Int J Pediatr Adolesc Med. 2 (1): 38–43. doi:10.1016/j.ijpam.2015.03.001. PMID 30805435.
- ↑ Chung KF, Bolser D, Davenport P, Fontana G, Morice A, Widdicombe J (April 2009). "Semantics and types of cough". Pulm Pharmacol Ther. 22 (2): 139–42. doi:10.1016/j.pupt.2008.12.008. PMID 19136069.
- ↑ Polverino M, Polverino F, Fasolino M, Andò F, Alfieri A, De Blasio F (June 2012). "Anatomy and neuro-pathophysiology of the cough reflex arc". Multidiscip Respir Med. 7 (1): 5. doi:10.1186/2049-6958-7-5. PMID 22958367.
- ↑ "Acute cough in children".
- ↑ Kwon NH, Oh MJ, Min TH, Lee BJ, Choi DC (May 2006). "Causes and clinical features of subacute cough". Chest. 129 (5): 1142–7. doi:10.1378/chest.129.5.1142. PMID 16685003.
- ↑ Bergamini M, Kantar A, Cutrera R, Interest Group I (2017). "Analysis of the Literature on Chronic Cough in Children". Open Respir Med J. 11: 1–9. doi:10.2174/1874306401711010001. PMID 28553418. Vancouver style error: initials (help)
- ↑ Stroud RH, Friedman NR (2001). "An update on inflammatory disorders of the pediatric airway: epiglottitis, croup, and tracheitis". Am J Otolaryngol. 22 (4): 268–75. doi:10.1053/ajot.2001.24825. PMID 11464324.
- ↑ Solomon P, Weisbrod M, Irish JC, Gullane PJ (1998). "Adult epiglottitis: the Toronto Hospital experience". J Otolaryngol. 27 (6): 332–6. PMID 9857318.
- ↑ Cherry, James D. (2008). "Croup". New England Journal of Medicine. 358 (4): 384–391. doi:10.1056/NEJMcp072022. ISSN 0028-4793.
- ↑ Bellamy EA, Johnston ID, Wilson AG (1987). "The chest radiograph in whooping cough". Clin Radiol. 38 (1): 39–43. PMID 3816065.
- ↑ "Pertussis | Whooping Cough | Clinical | Information | CDC".
- ↑ "What is LPR? | American Academy of Otolaryngology-Head and Neck Surgery".
- ↑ Noordzij JP, Khidr A, Desper E, Meek RB, Reibel JF, Levine PA (2002). "Correlation of pH probe-measured laryngopharyngeal reflux with symptoms and signs of reflux laryngitis". Laryngoscope. 112 (12): 2192–5. doi:10.1097/00005537-200212000-00013. PMID 12461340.
- ↑ Eccles R (2005). "Understanding the symptoms of the common cold and influenza". Lancet Infect Dis. 5 (11): 718–25. doi:10.1016/S1473-3099(05)70270-X. PMID 16253889.
- ↑ Kim EA, Lee KS, Primack SL, Yoon HK, Byun HS, Kim TS, Suh GY, Kwon OJ, Han J (2002). "Viral pneumonias in adults: radiologic and pathologic findings". Radiographics. 22 Spec No: S137–49. doi:10.1148/radiographics.22.suppl_1.g02oc15s137. PMID 12376607.
- ↑ Meltzer EO, Hamilos DL (2011). "Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines". Mayo Clin Proc. 86 (5): 427–43. doi:10.4065/mcp.2010.0392. PMC 3084646. PMID 21490181.
- ↑ Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, Orlandi RR, Palmer JN, Patel ZM, Peters A, Walsh SA, Corrigan MD (2015). "Clinical practice guideline (update): adult sinusitis". Otolaryngol Head Neck Surg. 152 (2 Suppl): S1–S39. doi:10.1177/0194599815572097. PMID 25832968.
- ↑ Ukena D, Fishman L, Niebling WB (2008). "Bronchial asthma: diagnosis and long-term treatment in adults". Dtsch Arztebl Int. 105 (21): 385–94. doi:10.3238/arztebl.2008.0385. PMC 2696883. PMID 19626179.
- ↑ Wenzel RP, Fowler AA (2006). "Clinical practice. Acute bronchitis". N. Engl. J. Med. 355 (20): 2125–30. doi:10.1056/NEJMcp061493. PMID 17108344.
- ↑ Brusasco V, Martinez F (2014). "Chronic obstructive pulmonary disease". Compr Physiol. 4 (1): 1–31. doi:10.1002/cphy.c110037. PMID 24692133.
- ↑ Qaseem A, Snow V, Shekelle P, Sherif K, Wilt TJ, Weinberger S, Owens DK (2007). "Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 147 (9): 633–8. PMID 17975186.
- ↑ Brightling CE (2006). "Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based clinical practice guidelines". Chest. 129 (1 Suppl): 116S–121S. doi:10.1378/chest.129.1_suppl.116S. PMID 16428700.
- ↑ Cho J, Choi SM, Lee J, Park YS, Lee SM, Yoo CG; et al. (2018). "Clinical Outcome of Eosinophilic Airway Inflammation in Chronic Airway Diseases Including Nonasthmatic Eosinophilic Bronchitis". Sci Rep. 8 (1): 146. doi:10.1038/s41598-017-18265-2. PMC 5760521. PMID 29317659.
- ↑ King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW (2006). "Characterisation of the onset and presenting clinical features of adult bronchiectasis". Respir Med. 100 (12): 2183–9. doi:10.1016/j.rmed.2006.03.012. PMID 16650970.
- ↑ Rossi A, Butorac-Petanjek B, Chilosi M, Cosío BG, Flezar M, Koulouris N; et al. (2017). "Chronic obstructive pulmonary disease with mild airflow limitation: current knowledge and proposal for future research - a consensus document from six scientific societies". Int J Chron Obstruct Pulmon Dis. 12: 2593–2610. doi:10.2147/COPD.S132236. PMC 5587130. PMID 28919728.
- ↑ Hewlett JC, Rickman OB, Lentz RJ, Prakash UB, Maldonado F (2017). "Foreign body aspiration in adult airways: therapeutic approach". J Thorac Dis. 9 (9): 3398–3409. doi:10.21037/jtd.2017.06.137. PMC 5708401. PMID 29221325.
- ↑ Rafanan AL, Mehta AC (2001). "Adult airway foreign body removal. What's new?". Clin. Chest Med. 22 (2): 319–30. PMID 11444115.
- ↑ Haddadi S, Marzban S, Nemati S, Ranjbar Kiakelayeh S, Parvizi A, Heidarzadeh A (2015). "Tracheobronchial Foreign-Bodies in Children; A 7 Year Retrospective Study". Iran J Otorhinolaryngol. 27 (82): 377–85. PMC 4639691. PMID 26568942.
- ↑ Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, Lohr KN (2004). "Diagnosis and testing in bronchiolitis: a systematic review". Arch Pediatr Adolesc Med. 158 (2): 119–26. doi:10.1001/archpedi.158.2.119. PMID 14757603.
- ↑ "www.nice.org.uk".
- ↑ Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ (2000). "Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America". Clin. Infect. Dis. 31 (2): 347–82. doi:10.1086/313954. PMID 10987697.
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