Structural Lung Disease Research Articles

Review Series: What goes around, comes around: childhood influences on later lung health?: Long-term follow-up of infants with lung disease of prematurity

The incidence of live preterm birth is increasing and concomitantly the survival of preterm babies has increased over the last 30 years due to advances in neonatal care. Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal and/or neonatal lung injury following preterm birth and the pathology has also changed with changes in neonatal care. There are data suggesting that there is increased respiratory morbidity of ex-preterm subjects in childhood. It is only now that large populations of preterm subjects are reaching adulthood and may be at risk of persistent respiratory morbidity. This review will summarize the current knowledge in adulthood of respiratory sequelae following preterm birth; specifically it will review respiratory symptoms, pulmonary function, exercise capacity and structural lung disease as determined by high resolution computed tomography scans in ex-preterm survivors with and without BPD. Whether prematurity-related lung disease is associated with chronic obstructive airways disease will be discussed.

A CT Scan Score for the Assessment of Lung Disease in Children With Common Variable Immunodeficiency Disorders

The prevalence and severity of structural lung disease in children with common variable immunodeficiency (CVID) disorders is not well known, and a dedicated CT scanning protocol and CT scan scoring system have not been described in this category. This was a cohort study of 54 children (34 CVID, 20 CVID-like disorder) in a stable condition who underwent volumetric inspiratory and end-expiratory CT scans. Scans were scored for airway abnormalities, interstitial and parenchymal lung disease, and lymphadenopathy using a newly developed CT scan scoring system. Scores were normalized to a 0% to 100% scale. Observer agreement was assessed using an intraclass correlation coefficient (Ri). Prevalence and severity of CT scan abnormalities were calculated. Structural lung disease was common (85%-93%), but usually mild as reflected in the relatively low scores (bronchiectasis score 2.8% +/- 6.4%). Moderate-to-severe bronchiectasis was found in three (5%) patients. Expiratory air trapping was the most common finding, found in 71% to 80%, but often in a mild form; application of a cut off level of > 10% reduced its prevalence to 33% to 38%. In 9% to 15% of all patients, air trapping was the only abnormality. Multiple lung nodules were seen in 24% to 25% and could disappear after corticosteroid treatment. Observer agreement was moderate (Ri 0.6-0.79) to good (Ri > 0.8) for all items and the composite scores, except airway wall thickening. In children with CVID disorders, mild structural lung disease is common. Expiratory CT scans show the most frequent abnormality, air trapping. The occurrence of (silent) lung disease progression and the clinical impact of CT scans require further investigations.

Sensitivity of lung clearance index and chest computed tomography in early cf lung disease

It is widely accepted that CF lung disease starts before clinical symptoms become apparent or spirometry deteriorates. Computed chest tomography (CT) is the reference method for identifying structural changes in CF; however, radiation exposure limits its use as a monitoring tool. It has been suggested that the Lung Clearance Index (LCI) measured by Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity is a more sensitive surrogate marker than spirometry allowing non-invasive monitoring of CF lung disease. The aim of this study was to prospectively investigate the diagnostic accuracy of the LCI in comparison to CT in CF patients with early lung disease and normal FEV(1) (>80% pred.). MBW and ultra-low-dose CT were performed in 34 patients (6-26 years). LCI was abnormal in 76.5% subjects. LCI and CT correlated significantly in 82.3%. LCI was related to presence and extent of structural lung changes observed on CT with a sensitivity of 88%. Diagnostic accuracy of the LCI for detecting CF lung disease in patients with normal FEV(1) was good when compared to CT. Results indicate that structural changes are unlikely if a normal LCI is measured. We speculate that serial measurements of the LCI for assessing ventilation inhomogeneity may help to identify early structural lung disease and help to reduce the individual cumulative radiation dose. The LCI may be a suitable surrogate marker for monitoring progression of CF lung disease and effect of treatment in both, clinical care and research settings.

Lessons Learned from Surveillance of Antimicrobial Susceptibilities of Pseudomonas aeruginosa at a Large Academic Medical Center.

This research report assessed the differences in resistance rates and antimicrobial usage-versus-susceptibility relationships of Pseudomonas aeruginosa found in various hospital patient care areas. A simplified case control study was also performed to identify patient-specific risk factors associated with cefepime-resistant P. aeruginosa isolates. Last, we determined the consequence of combining mucoid and non-mucoid derived antimicrobial susceptibilities of P. aeruginosa into hospital antibiograms. Overall, susceptibility rates remained lower in the intensive care units (ICUs) compared to the non-ICU patient care areas, except for cefepime over the last time period. Cefepime utilization and antimicrobial-resistance rates among P. aeruginosa isolates had a significant relationship. Decreased meropenem exposure was associated with lower resistance rates relative to cefepime. Risk factors independently associated with cefepime-resistant P. aeruginosa were structural lung disease, ICU admission, recent third generation cephalosporin use, frequent hospital admission and non-urine isolates. Large and statistically significant differences were observed between non-mucoid and combined percent susceptibility data for aminoglycosides. To control antimicrobial resistance and optimize initial empiric antimicrobial therapy, antimicrobial susceptibility and utilization patterns in specific patient care areas should be monitored and risk factors for antimicrobial resistance should be assessed. Mucoid strains of P. aeruginosa should not be included into antimicrobial susceptibility data as this may underestimate activity of most antipseudomonal agents.

Needle Aspiration of Spontaneous Pneumothorax

A 25-year-old man with a medical history of mild intermittent asthma and daily tobacco use presented to the emergency department with 6 hours of sudden-onset dyspnea and right-sided pleuritic chest pain. He had no fevers, chills, cough, or recent trauma. He was in no respiratory distress and was alert and oriented to person, place, and time. His vital signs were temperature 98.2°F, heart rate 56 beats/min, respiratory rate 18 breaths/min, blood pressure 112/71 mm Hg, and oxygen saturation 99% while breathing room air. Upright end-expiratory chest radiography demonstrated a small right-sided pneumothorax (Figure 1). Noncontrast computed tomography (CT) demonstrated a moderate right-sided pneumothorax and multiple small peripheral blebs (Figure 2). Given the patient’s underlying structural lung disease evident on CT, a tube thoracostomy was planned. The patient, however, requested that an attempt at needle aspiration be performed. Before the procedure, the emergency physician performed a bedside lung ultrasound using a 10–5 MHz linear array transducer (SonoSite MTurbo, Bothell, WA). Examination of the right anterior chest wall demonstrated absent pleural sliding (Video Clip S1). After written informed consent was obtained, the patient underwent aspiration of the right-sided pneumothorax using a single-lumen catheter with a three-way stopcock and syringe (Video Clip S2). During the procedure, a repeat ultrasound examination demonstrated partial resolution of the pneumothorax, with visualization of the “lung point” sign (Video Clip S3); pleural sliding was visualized along one side of an interspace, with absent pleural sliding on the other side of the same interspace (representing the border of the pneumothorax). After repositioning of the catheter and aspiration of an additional 100 mL of air, ultrasound examination confirmed return of normal pleural sliding anteriorly (Video Clip S4). Posteroanterior chest radiograph demonstrates small right-sided pneumothorax. Noncontrast CT scan demonstrates moderate right-sided pneumothorax with peripheral bleb. Chest radiography was performed 30 minutes after completion of the procedure and demonstrated reaccumulation of the pneumothorax. A tube thoracostomy was performed, resulting in complete resolution of the pneumothorax, and the patient was admitted to the cardiothoracic surgery service for further management. While primary spontaneous pneumothorax can be managed with needle aspiration or tube thoracostomy with similar results,1 patients with secondary spontaneous pneumothoraces (pneumothoraces associated with underlying structural lung disease) are more likely to have persistent air leaks that result in recurrence of their pneumothoraces. While needle aspiration can be safely performed in these cases, tube thoracostomy will often be necessary for definitive treatment. Video Clip S1. Absent pleural sliding. Video Clip S2. Aspiration of the right-sided pneumothorax using a single lumen catheter with a three-way stopcock and syringe. Video Clip S3. Repeat ultrasound examination demonstrated partial resolution of the pneumothorax, with visualization of the “lung point” sign. Video Clip S4. Confirmation of return of normal pleural sliding anteriorly. The video clip is in QuickTime. Please note: Wiley Periodicals Inc. is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Bacteriological and clinical profile of Community acquired pneumonia in hospitalized patients

The aim of our study was to obtain comprehensive insight into the bacteriological and clinical profile of community-acquired pneumonia requiring hospitalization. The patient population consisted of 100 patients admitted with the diagnosis of community-acquired pneumonia (CAP), as defined by British Thoracic society, from December 1998 to Dec 2000, at the Sher- i-Kashmir institute of Medical Sciences Soura, Srinagar, India. Gram negative organisms were the commonest cause (19/29), followed by gram positive (10/29). In 71 cases no etiological cause was obtained. Pseudomonas aeruginosa was the commonest pathogen (10/29), followed by Staphylococcus aureus (7/29), Escherichia coli (6/29), Klebsiella spp. (3/29), Streptococcus pyogenes (1/29), Streptococcus pneumoniae (1/29) and Acinetobacter spp. (1/29). Sputum was the most common etiological source of organism isolation (26) followed by blood (6), pleural fluid (3), and pus culture (1). Maximum number of patients presented with cough (99%), fever (95%), tachycardia (92%), pleuritic chest pain (75%), sputum production (65%) and leucocytosis (43%). The commonest predisposing factors were smoking (65%), COPD (57%), structural lung disease (21%), diabetes mellitus (13%), and decreased level of consciousness following seizure (eight per cent) and chronic alcoholism (one per cent). Fourteen patients, of whom, nine were males and five females, died. Staphylococcus aureus was the causative organism in four, Pseudomonas in two, Klebsiella in one, and no organism was isolated in seven cases. The factors predicting mortality at admission were - age over 62 years, history of COPD or smoking, hypotension, altered sensorium, respiratory failure, leucocytosis, and staphylococcus pneumonia and undetermined etiology. The overall rate of identification of microbial etiology of community-acquired pneumonia was 29%, which is very low, and if serological tests for legionella, mycoplasma and viruses are performed the diagnostic yield would definitely be better. This emphasizes the need for further studies (including the serological tests for Legionella, mycoplasma and viruses) to identify the microbial etiology of CAP.

Emergency Use of an Endobronchial One-Way Valve in the Management of Severe Air Leak and Massive Subcutaneous Emphysema

Bronchopleural (BPF) and alveolar-pleural (APF) fistulas are frequently encountered in clinical practice with persistent air leaks that can lead to significant morbidity, prolonged hospital stay, and potentially increased mortality. BPF and APF are commonly related to pulmonary resections. Other etiologies include minimally invasive procedures (thoracentesis and image-guided biopsies), and spontaneous fistulas related to an underlying structural lung disease (e.g., emphysema) or a necrotizing pulmonary process (e.g., infection or malignancy). Radiofrequency ablation for pulmonary malignancies is an effective modality that can rarely lead to APF with persistent air leak. Surgical intervention remains the standard treatment option for BPF and APF. A variety of minimally invasive bronchoscopic approaches can be considered for selected nonsurgical candidates. The use of one-way endobronchial valves to manage severe and persistent air leaks can be considered a minimally invasive option in selected patients. The valves selectively block inspiratory airflow to a specific segmental or subsegmental airway but allow expiratory flow with drainage of air and secretions from the corresponding distal airways and lung parenchyma.

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

CT-detected early structural lung disease is progressive in infants and preschool children

CT-detected early structural lung disease is progressive in infants and preschool children

Bronchiectasis in an asymptomatic infant with cystic fibrosis diagnosed following newborn screening

Many countries have introduced newborn screening for cystic fibrosis to facilitate diagnosis prior to the development of lung disease. Although most infants with cystic fibrosis are asymptomatic from a respiratory point of view at diagnosis, structural lung disease has been detected by computed tomography. We present a case of an asymptomatic infant with cystic fibrosis diagnosed following newborn screening who had endobronchial infection with Pseudomonas aeruginosa and radiological evidence of bronchiectasis at 3 months of age.

Current Treatment of Pseudomonal Infections in the Elderly

Pseudomonas aeruginosa infections have emerged as a major infectious disease threat in recent decades as a result of the significant mortality of pseudomonal pneumonia and bacteraemia, and the evolving resistance exhibited by the pathogen to numerous antibacterials. Pseudomonas possesses a large genome; thus, the pathogen is environmentally adaptable, metabolically flexible, able to overcome antibacterial pressure by selecting for resistant strains and even able to accumulate resistance mechanisms, leading to multidrug resistance (MDR), an increasingly recognized therapeutic challenge. In fact, most research currently does not focus on maximizing the efficacy of available antibacterials; rather, it focuses on maximizing their ecological safety. The elderly population may be particularly prone to pseudomonal infection as a result of increased co-morbidities (such as diabetes mellitus and structural lung disease), the presence of invasive devices such as urinary catheters and feeding tubes, polypharmacy that includes antibacterials, and immune compromise related to age. However, age per se, as well as residence in nursing homes, may not predispose individuals to an increased risk for pseudomonal infection. On the other hand, age has been repeatedly outlined as a risk factor for MDR pseudomonal infections. The severity of pseudomonal infections necessitates prompt administration of appropriate antibacterials upon suspicion. Progress has been made in recognizing risk factors for P. aeruginosa infections both in hospitalized and community-residing patients. Antimicrobial therapy may be instituted as a combination or monotherapy: the debate cannot be definitively resolved since the available data are extracted from studies with varying targeted populations and varying definitions of response, adequacy and MDR. Empirical combination therapy maximizes the chances of bacterial coverage and exerts a lower resistance selection pressure. Although associated with increased percentages of adverse events, mainly as a result of the included aminoglycosides, empirical combination therapy seems a reasonable choice. Upon confirmation of Pseudomonas as the causative agent and awareness of its susceptibility profile, monotherapy is advocated by many, but not all, experts. Infections involving MDR strains can be treated with colistin, which has adequate efficacy and few renal adverse events, or doripenem. In the elderly, in addition to making dose modifications that are needed because of loss of renal function, the prescriber should be more cautious about the use of aminoglycoside-containing regimens, possibly replacing them with a combination of quinolone and a beta-lactam, notwithstanding the possible increased pressure for selection of resistance with the latter combination.

Lung Disease at Diagnosis in Infants with Cystic Fibrosis Detected by Newborn Screening

The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

Semiinvasive Aspergillosis: A Diagnosis to Consider in a Seemingly Immunocompetent Patient with a Pulmonary Nodule, Haemoptysis and Structural Lung Disease.

Semiinvasive pulmonary aspergillosis is an indolent form of pulmonary aspergillosis, which is seen mainly in patients who are mildly immunocompromised with underlying chronic lung diseases. This syndrome is rare, and the available literature is based on case reports and small case series. We describe here a patient with a semiinvasive aspergillosis associated with a probable idiopathic pulmonary fibrosis.

Usefulness of Semi-quantitative Procalcitonin Assay in Critically Ill Patients with Bacterial Pneumonia

Background : In pulmonary infection, serum procalcitonin levels increase rapidly, probably in response to sepsis-related cytokine release from neuroendocrine cells of bronchial epithelium and inflammatory cells. We applied procalcitonin assay in critically ill patients with bacterial pneumonia. Materials and Methods : Patients admitted to the intensive care unit (ICU) and show diffuse infiltrations in their chest X-ray were included. Quantitative bronchoalveolar lavage (BAL) culture ( 10 ≥ 4 CFU/mL) was performed in all cases on the 5 th day of ICU admission. We excluded patients with structural lung disease, non-infectious lung infiltrations, and atypical infections such as Mycobacterium tuberculosis, Pneumocystis jiroveci , and viruses. Serum procalcitonin levels were measured semi-quantitatively by using PCT-Q kit. Results : A total of 28 adult patients (M:F=23:5) were included: 11 (39.3%) medically-ill patients, 7 (25%) sur - gically-ill patients, and 10 (35.7%) burn patients. Serum procalcitonin level was 0.5 ng/mL in half of the cases < (14/28) and 0.5 ng/mL in the remaining half of the cases. Compared to those with serum procalcitonin level of ≥ 0.5 ng/mL, patients with serum procalcitonin level of 0.5 ng/mL had more frequent mechanical ventilation, < ≥ higher CRP/APACHE II scores/number of organ failure ( P 0.05), and showed increased tendency for death < (P=0.052). Positive bacterial BAL cultures were noted in 17 cases (60.7%). Of these, 7 cases (41.2%) showed serum procalcitonin level 0.5 ng/mL. ≥ Conclusions : High serum procalcitonin level seems to be closely associated with the severity and poor prognosis in critically ill patients with bacterial pneumonia. However, pneumonia could not be excluded with low level of procalcitonin among ICU patients.

Structural and Functional Lung Disease in Primary Ciliary Dyskinesia

High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural abnormalities; to evaluate the correlation among HRCT scan scores, spirometry findings, and clinical data; and to compare the PCD scores with those of age-matched and sex-matched cystic fibrosis (CF) patients. Twenty PCD patients (age range, 4.6 to 27.5 years) underwent HRCT scanning, spirometry, and deep throat or sputum culture. A modified Brody score was used to assess bronchiectasis, mucous plugging, peribronchial thickening, parenchyma abnormalities, and mosaic perfusion. The total HRCT scan score was 6% of the maximal score (range, 0.5 to 25.5). Subscores were as follows: bronchiectasis, 5.6%; mucous plugging, 5.6%; peribronchial thickening, 8.3%; parenchyma, 3%; and mosaic perfusion, 0%. The prevalence of lung changes were as follows: bronchiectasis, 80%; peribronchial thickening, 80%; mucous plugging, 75%; parenchyma, 65%; and mosaic perfusion, 45%. Sixteen of 19 PCD patients had positive culture findings, and the most common pathogen found was Haemophilus influenzae (84%). The total HRCT scan score was significantly related to age (p = 0.006), FEV(1) (p = 0.02), and FVC (p = 0.02). The bronchiectasis subscore was significantly related to FEV(1) (p = 0.04) and FVC (p = 0.03). In CF patients, the total HRCT scan score was significantly higher than that in PCD patients (p = 0.02). PCD patients show significantly lower pulmonary HRCT scan scores than CF patients. The PCD total and bronchiectasis scores correlate with spirometry findings. The PCD HRCT scan score might be used for longitudinal assessment and/or represent an outcome surrogate in future studies.

Role of high-resolution computed tomography in the detection of early cystic fibrosis lung disease

High-resolution computed tomography (HRCT) has been demonstrated to be sensitive at detecting early lung disease in cystic fibrosis (CF), often before it is apparent clinically. There is emerging evidence that structural changes in the lung occur earlier in life than previously appreciated. Despite this, the role of HRCT in young children with CF has yet to be defined, principally because the repeated exposure of children to X-ray doses several multiples that of a standard chest X-ray raises the concern of the long-term risks of ionizing radiation. With the challenges of acquiring HRCT images in young children in mind, we review scanning protocols and settings specific to young children, and review the best available evidence that describes early structural lung disease in young children with CF. The role of CT scoring and quantitative measures of CF lung disease are reviewed. The challenge for the future is to develop techniques that provide clinically useful information at the lowest possible radiation risk.

Susceptibility to nontuberculous mycobacterial lung disease: Table 1—

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study. Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have become recognised since the 1980s, in particular middle-aged nonsmokers without previous lung disease (a group including those with Lady Windermere syndrome) and patients with genetically determined defects of cell-mediated immunity, including abnormalities of the interleukin-12/interferon-gamma axis, certain human leukocyte antigen alleles, cystic fibrosis transmembrane conductance regulator mutations, and polymorphisms of solute carrier 11A1 (or natural resistance-associated macrophage protein 1) and the vitamin D receptor. Information is also accruing about acquired systemic causes of susceptibility to NTMLD, including inhibitory antibodies directed against interferon-gamma, post-menopausal waning of endogenous oestrogen levels, coeliac disease and exposure to use of dietary phyto-oestrogens. It is not known whether immunosuppressive factors, such as oral corticosteroid treatment, chronic renal failure, diabetes mellitus and other known risk factors for pulmonary tuberculosis, are also risk factors for the development of NTMLD. Caution is appropriate in managing such patients.

An aspergilloma caused byAspergillus flavus

Chronic pulmonary aspergillosis is broad term encompassing chronic cavitary, chronic fibrosing pulmonary aspergillosis and aspergilloma. All affect patients with structural lung diseases and many have subtle genetic immune defects. Almost all cases are caused by Aspergillus fumigatus. Here we report a patient with an aspergilloma which had Aspergillus flavus recovered from a surgical specimen and serum containing detectable precipitating antibody.

HAP/VAP: Simpler May Be Cetter

HAP/VAP: Simpler May Be Cetter

Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis

Background: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal...