Moraxella (Branhamella) catarrhalis: its isolation in the respiratory secretions of adult patients

OBJECTIVE: We have designed a retrospective study in order to know the clinical significance of the isolation of Moraxella (Branhamella) catarrhalis (MC) in respiratory specimens of adult hospitalized patients. METHODS: We performed a Gram stain and culture on blood-agar, MacConkey media and quantitative culture in chocolate-agar to all respiratory samples. In patients with a clinical diagnosis of pneumonia BCYE-alpha was added. During 2 years (1992-1993) MC was isolated in respiratory specimens from 52 patients. We revised the clinical history of all these patients. RESULTS: MC was isolated in 60 respiratory specimens (sputum and/or tracheobronchial aspirates) from 52 patients. The Gram stain showed gram-negative cocci in 77% and gram-positive cocci in 17% of the cases. MC grew in pure culture in 28 specimens (46.6%). In 23% of cases MC was isolated with Streptococcus pneumoniae and in 21% with Haemophilus influenzae. Fifty-two stocks (86.6%) produced beta-lactamase. Twelve patients had a clinical diagnosis of pneumonia, 8 of them had an underlying chronic respiratory disease. Other 24 patients with an underlying chronic respiratory disease had a bronchial infection as a cause of exacerbation of their respiratory disease. Seven patients without an underlying chronic respiratory disease had a clinical episode of acute bronchitis. Finally, in 9 patients the isolation of MC was considered a colonization. CONCLUSIONS: In 17% cases MC was identified as a gram-positive cocci in the Gram stain, which may cause false diagnosis. The etiological importance of MC in episodes of acute exacerbation of patients with an underlying chronic respiratory disease is high.     

The community hospital: a three-year study

In a three-year period a community hospital of 40 beds discharged 2086 patients, their mean length of stay being 14.8 days. Some 68% of the patients treated were over 65, and 8.9% died in hospital. While the most common diagnosis on admission was disease of the respiratory tract, this does not indicate the actual cause of admission. For 142 patients from one practice this was acute illness in 44% of the cases, assessment in 20%, and a need for nursing care in 36%. If the community hospital had not been available about half these patients would have been admitted to the general hospital.     

Salmonella lung involvement in patients with HIV infection

STUDY OBJECTIVE: To determine the frequency, clinical features, and outcome of lung involvement in HIV-infected patients having nontyphoid strains of Salmonella bacteremia. DESIGN: A retrospective clinical study. PATIENTS AND SETTING: We studied the records of all HIV-infected patients with Salmonella bacteremia diagnosed at a university tertiary hospital from January 1987 to December 1995. RESULTS: Lung involvement was found in 18 (35.3%) of 51 HIV-infected individuals with Salmonella bacteremia. Six of 18 (33.3%) were diagnosed as having definite Salmonella pulmonary infection by isolation of Salmonella from respiratory specimens, while probable Salmonella lung disease was considered in two patients who developed lung abscesses without the identification of any pathogen. Predisposing factors for focal disease, such as prior lung disease or Salmonella serotype, were equally prevalent regardless of the presence of Salmonella pulmonary involvement. Cavitary infiltrates or abscess formation were seen in five of the eight patients. With the exception of one patient coinfected with Nocardia asteroides who died 1 month later, all patients were cured with antibiotic treatment. Superinfection with other pulmonary pathogens (10 cases, 56%) was more frequent than Salmonella pneumonia; the most frequent alternative diagnosis was Pneumocystis carinii pneumonia (5 cases, 28%), pyogenic bacterial infection (17%), and tuberculosis (11%). CONCLUSIONS: In HIV-infected patients with Salmonella bacteremia, lung involvement is frequent, although there were no significant factors to explain this association. Cavitary disease was the most common radiologic pattern, and focal lung disease due to Salmonella does not seem to be associated with a worse prognosis. Coinfection and superinfection with other respiratory pathogens are more common than isolated Salmonella lung disease, and therefore, additional diagnostic procedures must be considered in the evaluation of these patients.     

Prognostic factors and etiology in patients with severe community-acquired pneumonia admitted at the ICU. Spanish multicenter study. Study Group on Severe Community-Acquired Pneumonia in Spain

OBJECTIVE: To determine the techniques used for the etiological diagnosis of community-acquired pneumonia in patients admitted to the intensive care unit (ICU) and to describe the predominant causative organisms as well as prognostic factors of ICU mortality. PATIENTS AND METHODS: A total of 262 patients with community-acquired pneumonia admitted to 26 ICUs between 1 November of 1991 and 31 October of 1992 were included in a prospective, open, multicenter study. RESULTS: The diagnostic techniques most frequently used were blood culture (243 cases) and simple tracheal aspirate (166 cases). Simple tracheal aspirate (58.4%), bronchoalveolar lavage (47.7%), and protected-specimen brush (44.2%) were the techniques that showed the highest diagnostic reliability. In 220 cases, techniques considered of high diagnostic probability were employed. With the use of these procedures, the most frequent causative pathogens were Streptococcus pneumoniae (13.6%) and Legionella pneumophila (9.5%). In 100 cases (45.5%), no pathogen was isolated. A total of 88 patients (33.6%) died during the ICU stay. Predictive variables of poor outcome selected by means of a multivariate analysis were as follows: multisystemic failure (OR = 28.6; 95% CI: 12.8-65.1; p = 0.0001), APACHE II at the time of ICU admission (OR = 5.3; 95% CI: 2.5-11.3; p = 0.0001), progression and/or spread of lung infection (OR = 4.5; 95% CI: 2.4-8.4; p = 0.0001), and shock on admission (OR = 8.48; 95% CI: 4.5-15.9; p = 0.0001). CONCLUSIONS: In 45.5% of patients with community-acquired pneumonia admitted to ICU, no causative pathogen was identified. The prognosis of these patients was influenced by the severity of disease assessed by APACHE II score and presence of multisystemic failure and shock at the time of ICU admission.     

Bacteremic hemophilus influenzae pneumonia in adults. A report of 24 cases and a review of the literature

Twenty-four cases of Hemophilus influenzae pneumonia diagnosed by positive blood or pleural fluid cultures are compared to 43 cases previously reported in the literatrue. Frequently associated illnesses in both series include alcoholism, chronic airways obstruction and preceding respiratory tract infection. Moderate temperature elevation and slight leukocytosis were common on admission in both groups. Chest roentgenograms in our series revealed both bronchopneumonia (75 per cent) and lobar consolidation (38 per cent). Pleural disease occurred frequently, with two empyemas noted on admission and nine additional effusions developing during therapy. Treatment of choice was ampicillin. All five patients who did not receive ampicillin died, whereas 16 to 19 who received this drug survived. High mortality (33 per cent) in our series may be attributed to the advanced age of the patients and the presence of associated illnesses. In addition, a 10 year review suggests a true increase in the incidence of H. influenzae pneumonia in adults.     

Outbreak of adenovirus 35 pneumonia among adult residents and staff of a chronic care psychiatric facility

Outbreaks of acute respiratory disease caused by adenovirus are rarely documented in civilian populations, and adenovirus 35 is an uncommon serotype best recognized as a cause of serious disease in immunocompromised patients. An outbreak of adenovirus 35 pneumonia among residents and staff of a chronic care psychiatric facility was investigated. Fourteen (26%) of 53 residents and 4 (2%) of approximately 200 staff had radiographically confirmed pneumonia. Thirteen (93%) of 14 residents with pneumonia were hospitalized, 5 (36%) required mechanical ventilation, and 1 (7%) died. One staff member was hospitalized. Adenovirus infection was diagnosed in 17 (94%) persons with pneumonia by culture or serology and was confirmed as adenovirus 35 infection in 8 persons. Residents with pneumonia had resided at the facility longer than other residents. Chronic illness was not a risk factor for severe disease. Crowding and poor hygienic behaviors probably facilitated transmission among residents.     

Multiple cases of life-threatening adenovirus pneumonia in a mental health care center

Eighteen cases of pneumonia developed during an outbreak of adenovirus infection in a chronic psychiatric care facility. The six patients most severely affected were admitted to the intensive care unit (ICU) at our institution. Four of these patients developed septic shock. We report the presentation, disease progression, and response to treatment of these patients. Clinical features consisted of high fever, nonproductive cough, and dense lower lobe infiltrates. Laboratory abnormalities included transient fall in white blood cell and platelet counts, and elevations of transaminases, lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK). Five patients were intubated for hypoxemia and four developed the acute respiratory distress syndrome (ARDS) and septic shock (mean cardiac output, 14.1 +/- 1.3 L/min; cardiac index, 6.4 +/- 0.4 L/min/min2; systemic vascular resistance, 326 +/- 107 dyne cm/s2). All patients recovered and were discharged back to the chronic care facility except for one patient with chronic renal failure who died 2 mo after admission. Adenovirus (serotype 35) was isolated from the respiratory secretions of five patients and antibody titers increased 6-fold in the other. These patients constitute the largest series of patients with ARDS and septic shock caused by adenovirus pneumonia and the first outbreak of multiple cases of adenovirus pneumonia in immunocompetent civilian adults occurring from a single source.     

Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines

CONTEXT: Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established. OBJECTIVE: To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability. DESIGN: Prospective, multicenter, observational cohort study. SETTING: Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia. PATIENTS: Six hundred eighty-six adults hospitalized with community-acquired pneumonia. MAIN OUTCOME MEASURES: Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit. RESULTS: The median time to stability was 2 days for heart rate (< or =100 beats/min) and systolic blood pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24 breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability. CONCLUSIONS: Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management.     

Etiology of childhood pneumonia: serologic results of a prospective, population-based study

BACKGROUND: To investigate the etiology of pediatric community-acquired pneumonia, we conducted a prospective, population-based study covering the total population <15 years of age (n = 8851) in 4 municipalities in eastern Finland. MATERIALS AND METHODS: The number of patients was 201; chest radiographs were available for all cases and paired sera for serologic assays were available for >90% of cases. The methods included assays for antibody response to 3 pneumococcal antigens, specific pneumococcal immune complex assays and conventional antibody tests for mycoplasmal, chlamydial and viral infections. RESULTS: Serologic evidence of specific microbial etiology was obtained in 133 (66%) of the pneumonia patients. Bacterial infection was diagnosed in 102 cases (51%) and viral infection in 51 cases (25%). Streptococcus pneumoniae was the most common agent (57 cases; 28%), followed by Mycoplasma pneumoniae (44; 22%), respiratory syncytial virus (43; 21%) and Chlamydia spp. (29; 14%). Haemophilus influenzae was identified in only 6% and Moraxella catarrhalis in only 3% of the children. More than one specific infection was found in 51 patients (25%). The proportion of pneumococcal cases varied from 24 to 36% by age. Mycoplasma infections were seen mostly in patients > or =5 years and Chlamydia infections in patients > or =10 years of age. CONCLUSIONS: The results of our prospective, strictly population-based study confirm the importance of S. pneumoniae in the etiology of community-acquired pneumonia in children of all ages. M. pneumoniae and Chlamydia pneumoniae are important from the age of 5 years onwards.     

Community-acquired pneumonia: prospective study of 101 adult, immunocompetent patients for 1 year

BACKGROUND: A one year prospective study was carried out to assess the etiology of community-acquired pneumonia (CAP), and also to know the incidence, characteristics and evolution of infection by Chlamydia pneumoniae; and the effectiveness of DNA probes in CAP due to Mycoplasma pneumoniae and Legionella. METHODS: One hundred and ten patients with a diagnosis of CAP in the emergency department were studied. Serologic studies were performed, and also tests commonly used for the diagnosis of respiratory tract pathogens in respiratory samples, including serology and culture of Chlamydia pneumoniae and DNA probes for Mycoplasma pneumoniae and Legionella. RESULTS: In 72 cases (71.3%) some pathogen was found and in 5 cases more than one microorganism was involved. The etiology was bacterial in 31% of the cases, with S. pneumoniae being the most frequent (19 cases). Forty percent of the cases were "atypical" pneumonias with 33 cases of M. pneumoniae and 5 by Chlamydia pneumoniae. Diagnostic data of viral pneumonia were found in 2 cases. DNA probes were not useful for the diagnosis of pneumonia by Legionella pneumophila and had low effectiveness (31.8%) in Mycoplasma pneumoniae CAP. CONCLUSIONS: a) M. pneumoniae was the most frequent pathogen (33%). b) DNA probes for M. pneumoniae had low sensitivity in sputum (31.8%) and none in pharyngeal exudate. c) Acute infection by C. pneumoniae was diagnosed in 5 cases. Previous data of infection were recorded in 60.4% of the patients. d) Bacterial pneumonia (31%) was underestimated due to a low rate of bacteremic cases (7.9%) and the low number of positive cultures with definitive diagnostic value. e) The evolution was good except in two cases (death due to staphylococcal pneumonia with alcohol withdrawal syndrome and multiorganic failure by disseminated chicken-pox).     

The utility of chest radiography in the follow-up of pneumonia

AIM: We conducted this study to determine whether chest radiography was clinically useful in the follow-up of uncomplicated pneumonia affecting children aged between 6 weeks and 15 years. METHOD: We examined the case records of all 78 paediatric admissions for pneumonia to our hospital over one year. Thirteen children were excluded on account of age or other complicating factors. RESULTS: Of the 65 study cases, the mean age was 3.5 years (range 0.4-13 years). On admission 51 (79%) had cough, 53 (82%) fever, 53 (82%) tachypnoea and 50 (77%) had abnormal chest signs. Elevation of C reactive protein was recorded in 43 (66%) cases and leukocytosis in 42 (65%). All children received initial chest radiographs which showed unilobular/lobar changes in 34 (53%), bilobar changes in 19 (29%) and diffuse abnormalities in 7 (11%). Forty-one patients were followed up both clinically and radiologically, usually (31 cases) between four and six weeks after discharge. Thirty-seven children had no abnormal symptoms or signs and had normal chest radiographs. The remaining four had symptoms and signs, their radiographs showed either slight resolution or no change from the admission films. CONCLUSION: In cases of uncomplicated pneumonia, follow-up chest radiography should be deferred until at least four weeks after discharge and is not indicated if symptoms and signs are absent.     

A three-stage scheme for medical negligence

An eighteen-month prospective study designed to determine the incidence, etiology and prognosis of community acquired pneumonia (CAP) in adults requiring admission to hospital. METHODS: We studied 366 patients admitted to hospital after being diagnosed of CAP at the Emergency Room of a General Hospital. Standard laboratory methods were used for culture from blood and sputum, and serology tests for Legionella pneumophila. Mycoplasma pneumoniae, Chlamydia psittaci and Coxiella burnetti. Patients were evaluated until complete recovery, paying special attention to prognostic factors predictive of death. RESULTS: An etiological diagnosis was established in 99 patients (27.6%). Legionella pneumophila was the most common pathogen accounting for 30 cases (8.2%), followed by Streptococcus pneumoniae with 26 cases. 26 patients died (mortality rate of 7%); factors predictive of death included pre-existing disease, tachypnea and elevated blood urea nitrogen level. CONCLUSIONS: CAP represented 4.4% of admissions. Legionella pneumophila was the most frequently identified pathogen. If tachypnea and/or uremia are noted on admission, there is an increase in the risk of death.     

Usefulness of liver biopsy in the study of the pediatric patient. Review of 145 cases

There were reviewed 145 cases of children in which hepatic biopsy was done at the Hospital Infantil del Estado de Sonora, from 1978 to 1990. The larger age group were infants and preschool children (74.3 percent) males being predominant; signs and symptoms were related with hepatic illness, as well as the admission diagnoses. The indication of biopsy was for confirmation of liver disease in more than 50 percent, 37.1 percent for unknown diagnoses and 20.6 percent to look for liver disease by a systemic illness. The most usual procedure was percutaneous biopsy with Vim-Silverman needle in 111 cases (76.5 percent), in 23 percent, the biopsy was done by major surgical method. Nine percent of the children needed open surgical method after percutaneous biopsy. The time from the admission to biopsy performance in patients with neonatal hepatitis vs biliary atresia was 14 days. In other type of illness the time was 25 days. The morbidity was 1 percent. There was no mortality. The histopathologic diagnosis of liver diseases was done in 96 cases (66.7 percent) by this method in 31 children (21.3 percent) with investigation of jaundice (neonatal hepatitis vs biliary atresia). The diagnostic mistake in tissues obtained by percutaneous needle, was statistically significant (p < 0.05). Average hospitalization stay was less than two months in 70 percent of the cases.     

Myasthenia gravis presenting as isolated respiratory failure

We present 2 cases of idiopathic CD4+ T-lymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4+ T-lymphocyte count was 109/microl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4+ T-lymphocyte count was 238/microl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.     

Spermatogenesis in developmental age

The objective of this study was to define the type, the incidence and the outcome of early infectious complications (mean interval between day 1 post-BMT and the onset of fever was 9+/-3 days) occurring in granulocytopenic bone marrow transplant recipients, requiring medical intensive care unit admission. Over a five-years period, forty-one patients with microbiologically confirmed infection were enrolled, with a statistically significant higher frequency of allogeneic marrow transplant recipients (51%, p < 0.02). Infectious pneumonia occurred in 24 patients (59%), septicemia with septic shock in ten patients (24%), catheter-related infection in 5 patients (12%) and meningitis in 2 patients (5%) (p < 0.001). Twenty-six patients died (63%). Among the patients with confirmed infectious pneumonitis, which occurred most frequently in allogeneic marrow recipients (p < 0.02), 16 died (67%). This poor outcome was related to the requirement of mechanical ventilation. Eight patients (80%) with septicemia and septic shock and the two patients with meningitis died. Bacteria (Pseudomonas aeruginosa and Staphylococcal species) were the most common isolated in bronchoalveolar lavage fluid and blood cultures. We found a lower incidence of fungal or viral infections compared to previous studies. Empiric antimicrobial therapy in the cases of patients admitted in ICU may be included antibiotics anti-Pseudomonas and anti-Staphylococcus, as the ecology of hematology unit. The requirement of mechanical ventilation is the main adverse prognostic factor in transplanted patients. At ICU admission, patients with hepatic failure combined with respiratory failure represented a subgroup with a dismal prognosis.     

Validation of caregiver interviews to diagnose common causes of severe neonatal illness

The objective of this study was to validate retrospective caregiver interviews for diagnosing major causes of severe neonatal illness and death. A convenience sample of 149 infants aged < 28 days with one or more suspected diagnoses of interest (low birthweight/severe malnutrition, preterm birth, birth asphyxia, birth trauma, neonatal tetanus, pneumonia, meningitis, septicaemia, diarrhoea, congenital malformation or injury) was taken from patients admitted to two hospitals in Dhaka, Bangladesh. Study paediatricians performed a standardised history and physical examination and ordered laboratory and radiographic tests according to study criteria. With a median interval of 64.5 days after death or hospital discharge, caregivers of 118 (79%) infants were interviewed about their child's illness. Using reference diagnoses based on predefined clinical and laboratory criteria, the sensitivity and specificity of particular combinations of signs (algorithms) reported by the caregivers were ascertained. Sufficient numbers of children with five reference standard diagnoses were studied to validate caregiver reports. Algorithms with sensitivity and specificity > 80% were identified for neonatal tetanus, low birthweight/severe malnutrition and preterm delivery. Algorithms with specificities > 80% for birth asphyxia and pneumonia had sensitivities < 70%, or alternatively had high sensitivity with lower specificity. In settings with limited access to medical care, retrospective caregiver interviews provide a valid means of diagnosing several of the most common causes of severe neonatal illness and death.     

Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients: a clinical, radiological, microbiological, and epidemiological study

We prospectively studied features of pyogenic bacterial pneumonia in 263 consecutive human immunodeficiency virus-infected inpatients over a 6-month study period. Risk factors for bacterial pneumonia were examined by a case-control study that included 33 cases who presented with at least one episode of bacterial pneumonia and 80 controls without bacterial pneumonia. The estimated cumulative incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95% confidence interval [CI], 8.8-17.2). The 38 episodes of bacterial pneumonia that occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy lobar or diffuse infiltrates. Microbiological etiologies were obtained in 33 of the 38 episodes of bacterial pneumonia. Thirty-seven pathogens were identified, including Streptococcus pneumoniae (16, of which 12 had a decreased susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas aeruginosa (6). The risk factors for bacterial pneumonia that were identified after logistic regression included prior sinusitis within 1 month before admission (odds ratio [OR], 3.2; 95% CI, 1.1-9.1) and prior bacterial infection of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI, 1.1-8.3).     

Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients

Splenomegaly was studied retrospectively at the University of California, San Francisco, School of Medicine, on all patients (N = 2,056) for the years 1913 to 1962. The patients were classified into several diagnostic groups, and these groups were tested for statistical significance (chi(2)) with many clinical and laboratory variables to determine their predictive value. Hematologic disorders were associated with 57% of cases of splenomegaly and 81% of cases of massive splenomegaly. Among patients with splenomegaly, 19% had infectious diseases, 11% had hepatic diseases, and 9% had congestive or inflammatory disorders. The residual 4% were considered to have primary splenic disorders or a disorder of unknown cause. The commonest diseases associated with splenomegaly were hematologic (acute and chronic leukemias), infectious (malaria, endocarditis, and tuberculosis), hepatic (chronic liver disease), congestive (congestive heart failure), inflammatory (thyrotoxicosis), and other (cancers not metastatic to the spleen). The diseases most frequently associated with massive splenomegaly were the chronic leukemias. The disease with the highest incidence of massive splenomegaly was myelofibrosis (23 of 29 patients, 78%). Splenectomy was performed in 154 patients (7%), primarily for hematologic amelioration and hepatic hypersplenism. Hematologic diseases showed significant associations with lymphadenopathy, generalized lymphadenopathy, massive splenomegaly, and cytoses (P .001) and with progressive splenic enlargement (P < .02). Infectious diseases showed significant association with fever, and hepatic diseases showed significant association with abnormal results of liver function tests (P < .001). The findings of this retrospective study should be validated prospectively.     

Chlamydial pneumonia of infancy: further clinical observations

Two patients with chlamydial pneumonia of infancy are described. One recovered spontaneously without any specific antichlamydial treatment. The other, prior to a belated antimicrobial therapy, developed a persistent and protracted respiratory illness characterized by wheezing. Our observations suggest that: (1) untreated chlamydial pneumonia of infancy may spontaneously resolve, or may become a persistent and protracted disease, and (2) wheezing may be a very prominent manifestation of the disease and should be differentiated from wheezing due to bronchiolitis and bronchial asthma.