Evidence Of Small Airways Disease Research Articles

Development and Evaluation of a Small Airway Disease Index Derived From Modeling the Late-Expiratory Flattening of the Flow-Volume Loop.

Excessive decrease in the flow of the late expiratory portion of a flow volume loop (FVL) or “flattening”, reflects small airway dysfunction. The assessment of the flattening is currently determined by visual inspection by the pulmonary function test (PFT) interpreters and is highly variable. In this study, we developed an objective measure to quantify the flattening. We downloaded 172 PFT reports in PDF format from the electronic medical records and digitized and extracted the expiratory portion of the FVL. We located point A (the point of the peak expiratory flow), point B (the point corresponding to 75% of the expiratory vital capacity), and point C (the end of the expiratory portion of the FVL intersecting with the x-axis). We did a linear fitting to the A-B segment and the B-C segment. We calculated: 1) the AB-BC angle (∠ABC), 2) BC-x-axis angle (∠BCX), and 3) the log ratio of the BC slope over the vertical distance between point A and x-axis [log (BC/A-x)]. We asked an expert pulmonologist to assess the FVLs and separated the 172 PFTs into the flattening and the non-flattening groups. We defined the cutoff value as the mean minus one standard deviation using data from the non-flattening group. ∠ABC had the best concordance rate of 80.2% with a cutoff value of 149.7°. We then asked eight pulmonologists to evaluate the flattening with and without ∠ABC in another 168 PFTs. The Fleiss’ kappa was 0.320 (lower and upper confidence intervals [CIs]: 0.293 and 0.348 respectively) without ∠ABC and increased to 0.522 (lower and upper CIs: 0.494 and 0.550) with ∠ABC. There were 147 CT scans performed within 6 months of the 172 PFTs. Twenty-six of 55 PFTs (47.3%) with ∠ABC <149.7° had CT scans showing small airway disease patterns while 44 of 92 PFTs (47.8%) with ∠ABC ≥149.7° had no CT evidence of small airway disease. We concluded that ∠ABC improved the inter-rater agreement on the presence of the late expiratory flattening in FVL. It could be a useful addition to the assessment of small airway disease in the PFT interpretation algorithm and reporting.

EVALUATION OF SMALL AIRWAY REVERSIBILITY AMONG ASTHMATIC PATIENTS WITH NON-OBSTRUCTIVE PATTERNS OF SPIROMETRY

Background: Although the forced expiratory flow parameters are increasingly used in the diagnosis of small airway disease (SAD), the reversibility of these indicators is rarely described. The aim of this study is to evaluate the association of small airways reversibility with the presence of SAD and bronchodilator reversibility (BDR) of the proximal airways. Methods: The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the indicators of SAD (FEF25%, FEF50%, FEF75%, FEF25-75%, and FEF75-85%) were measured before and 20 minutes after salbutamol administration (200 mcg by using inhaler/Spacer). Positive BDR was accepted when FEV1 or FVC was increased ? 12% and &gt; 200 ml, indicating responsive proximal airways. Positive small airway reversibility was diagnosed when any of the small airway indicators is increased ? 30% above the baseline results. All measurements were performed with the All-flow spirometer (Clement Clarke International, Harlow, UK). Results: Evidence of SAD was found in 62.1% of all participants and in 75.2% of those who showed responsive proximal airways. The positive predictive value of the SAD in diagnosing responsive proximal airways was 67.8%. The reversibility of the small airway indicators showed insignificant association with the FEV1 or FVC BDR. The reversibility of FEF50%, FEF75% and FEF25-75% showed significant association with the diagnosis of SAD, with specificities ranging from 75.5%-81.1%. Conclusion: SAD has a significant association with positive reversibility of both the proximal and the peripheral airways. Further studies are needed to evaluate the clinical significance of positive small airway reversibility in the diagnosis and management of obstructive lung diseases. Keywords: Asthma; Small airway disease; Bronchodilator Reversibility, FEV1, FVC; FEF25-75%

A Novel Spirometric Measure Identifies Mild COPD Unidentified by Standard Criteria

In chronic obstructive pulmonary disease, both smaller and larger airways are affected. FEV1 mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow. In this study, the objective was to evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6seconds (FEV3/FEV6), and small airways measures and gas trapping at quantitative chest CT scanning, and clinical outcomes in the Genetic Epidemiology of COPD (COPDGene) cohort. Seven thousand eight hundred fifty-three current and ex-smokers were evaluated for airflow obstruction by using recently defined linear iteratively derived equations of Hansen et al to determine lower limit of normal (LLN) equations for prebronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6, and FEV3/FVC. General linear and ordinal regression models were applied to the relationship between prebronchodilator spirometric and radiologic and clinical data. Of the 10,311 participants included in the COPDGene phase I study, participants with incomplete quantitative CT scanning or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with FEV1/FVC greater than or equal to the LLN, 15.4%had abnormal FEV3/FEV6. Compared with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping; St. George's Respiratory Questionnaire score; modified Medical Research Council dyspnea score; and BMI, airflow obstruction, dyspnea, and exercise index and with shorter 6-min walking distance (all P< .0001) but not with CT scanning evidence of emphysema. Current and ex-smokers with prebronchodilator FEV3/FEV6 less than the LLN as the sole abnormality identifies a distinct population with evidence of small airways disease in quantitative CT scanning, impaired indexes of physical function and quality of life otherwise deemed normal by using the current spirometric definition.

Severe dyspnoea in a patient with chronic myelogenous leukaemia on a tyrosine kinase inhibitor

NR (Haematology fellow) : A 78-year-old male patient with chronic myelogenous leukaemia (CML) diagnosed initially in 2011 presented to the haematology clinic with fatigue and dyspnoea at rest and with...

Pleuroparenchymal fibroelastosis: Distinct pulmonary physiological features in nine patients.

Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia defined by pleural and subpleural parenchymal fibrosis predominantly in the upper lobes. Although the radiological and pathological characteristics of PPFE have become increasingly recognized, its pulmonary physiological features are not well understood. We reviewed nine patients with radiologically and histologically proven PPFE, and evaluated pulmonary physiological data. Of the nine patients, six were male and three were female. The median age at presentation was 61 years. Common symptoms were dyspnea on exertion, weight loss, and nonproductive cough. Recurrent pneumothorax was found in eight patients and pneumonia in four. Median pulmonary function test results were as follows: forced vital capacity, 55.4% predicted; total lung capacity (TLC), 67.1% predicted; residual volume (RV), 102.3% predicted; and RV/TLC, 143.6% predicted. RV/TLC was increased without evidence of small airway disease according to clinico-radiologic-pathologic evaluation. The median partial pressure of oxygen in arterial blood and the alveolar-arterial gradient of oxygen were within normal limits, although there was a slightly elevated partial pressure of carbon dioxide in arterial blood (PaCO2). PPFE progressed in all patients despite treatment with pirfenidone, corticosteroids, and immunosuppressive agents. Seven patients died during the follow-up, five because of hypercapnic respiratory failure. PPFE is characterized by severe mechanical restriction with high RV/TLC, causing increased PaCO2 and eventual hypercapnic respiratory failure. These physiological findings may be useful as an adjunct in the diagnosis of PPFE.

Pulmonary Involvement in Sjögren Syndrome

Sjögren syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic inflammation of exocrine glands and a variety of extraglandular sites. Lung involvement as defined by symptoms and either pulmonary function testing or radiographic abnormalities occurs in approximately 10 to 20% of patients. Subclinical lung disease is even more frequent and often includes evidence of small airways disease and airway inflammation. In general, patients will have evidence of both airway and interstitial lung disease by radiographs and pathology. Bronchiolitis and bronchiectasis are the most common airway manifestations while the interstitial pathologies associated with SS include nonspecific interstitial pneumonitis, usual interstitial pneumonitis, and lymphocytic interstitial pneumonitis. Patients with SS are also at an increased risk of lymphoma. A protean of other lung abnormalities including amyloidosis, granulomatous lung disease, pseudolymphoma, pulmonary hypertension, and pleural disease have been described.

Radiology of Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory distress syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a systemic infection that clinically manifests as progressive pneumonia. During the initial phases of infection the virus causes pauci-inflammatory alveolar and interstitial edema that result in imaging abnormalities dominated by ground glass opacities (GGO). Severe SARS cases can develop radiologic and pathologic findings of diffuse alveolar damage. Although radiologic evidence of acute bronchiolitis is absent, SARS-CoV also infects ciliated airway epithelium, probably accounting for respiratory transmissibility of the virus. Radiologic recovery from SARS can be complete, but computed tomography images often show persistent GGO and reticular opacities, some of which reflect pathologic findings of fibrosis. Long-term follow-up imaging of survivors shows gradual decrease of GGO and reticulation with persistent air trapping in some patients. The latter is evidence of small airway disease that is not radiologically evident at the onset of the disease.

Ventilatory Function in Experienced Recreational Scuba Divers: Evidence of Small Airways Disease?

Diving has shown long-term effects on respiratory function in trained professional divers, indicating the development of small airways disease. The results are more controversial in trained recreational divers because of the different degrees of exposure and training. The aim of this study was to investigate the effects of recreational diving on respiratory function in highly experienced divers. Volumes and expiratory flow rates were measured in 32 older recreational divers (51.6 +/- 7.4 years). The forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were higher (+ 4.9 % and + 6 %, respectively; p < 0.01) than the theoretical standards (ERS 93). These values tended to decrease more rapidly as the age advanced (age range: 43 - 73 years) (p < 0.05). Moreover, the mid-expiratory flows at 50 %, 25 % and 25 - 75 % of vital capacity (MEF(50 %), MEF(25 %) and MEF(25 - 75 %)) were significantly decreased. These early signs of decrease suggest slight small airways disease in older experienced recreational divers.

Functional Impairment in Emphysema: Contribution of Airway Abnormalities and Distribution of Parenchymal Disease

The aim of this study was to identify ancillary morphologic features on high-resolution CT that modify airflow obstruction and gas transfer levels in individuals with emphysema. The extent of emphysema on high-resolution CT was quantified by density masking in 101 patients. CT scans were evaluated for airway abnormalities (bronchial wall thickness, extent of bronchiectasis, bronchial dilatation, and evidence of small airways disease) and disease heterogeneity (uniformity, core-rind distribution, craniocaudal distribution, and lung texture). Stepwise regression analysis was used to determine CT features that influenced forced expiratory volume in 1 sec (FEV1) and the single-breath diffusing capacity for carbon monoxide (Dlco) for a given extent of emphysema. The extent of emphysema using automated estimation was 28.4% +/- 12.3% (mean +/- SD). On univariate analysis the extent of emphysema correlated strongly with FEV1 (R = -0.63, p < 0.0005) and Dlco (R = -0.63, p < 0.0005) levels. Stepwise regression analysis revealed that bronchial wall thickness and the extent of emphysema were the strongest independent determinants of FEV1 (model R2 = 0.49; p = 0.002 and < 0.001, respectively); the extent of bronchiectasis and degree of bronchial dilation did not separately influence FEV1 levels. The only morphologic features linked to Dlco levels on multivariate analysis were increasingly extensive emphysema and a higher proportion of emphysema in the core region (model R2 = 0.45; p < 0.001 and 0.002, respectively). The important additional CT abnormalities in individuals with emphysema that influence FEV1 and Dlco levels irrespective of disease extent are bronchial wall thickness and core-rind heterogeneity, respectively. These observations have implications for the accurate functional assessment of patients considered for lung volume reduction surgery.

Air Trapping in Sarcoidosis on Computed Tomography: Correlation with Lung Function

AIMS: To document the presence and extent of air trapping on high resolution computed tomography (HRCT) in patients with pulmonary sarcoidosis and correlate HRCT features with pulmonary function tests.METHODS: Twenty-one patients with pulmonary sarcoidosis underwent HRCT and pulmonary function assessment at presentation. Inspiratory and expiratory HRCT were assessed for the presence and extent of air trapping, ground-glass opacification, nodularity, septal thickening, bronchiectasis and parenchymal distortion. HRCT features were correlated with pulmonary function tests.RESULTS: Air trapping on expiratory HRCT was present in 20/21 (95%) patients. The extent of air trapping correlated with percentage predicted residual volume (RV)/total lung capacity (TLC) (r=0.499;P<0.05) and percentage predicted maximal mid-expiratory flow rate between 25 and 75% of the vital capacity (r=−0.54;P<0.05). Ground-glass opacification was present in four of 21 (19%), nodularity in 18/21 (86%), septal thickening in 18/21 (86%), traction bronchiectasis in 14/21 (67%) and distortion in 12/21 (57%) of patients; there were no significant relationships between these CT features and pulmonary function results.CONCLUSION: Air trapping is a common feature in sarcoidosis and correlates with evidence of small airways disease on pulmonary function testing.Davies, C. W. H. (2000). Clinical Radiology55, 217–221.

Multi-Modality Imaging: The Use of Single Photon Emission Computed Tomography and Magnetic Resonance Imaging to Assess Regional Intra-Pulmonary Deposition of Nebulised Aerosols

ABSTRACT Single Photon Emission Computed Tomography (SPECT) is now accepted as one method of providing 3-D images of an inhaled radioaerosol. Using SPECT, we have reconstructed 3-D images incorporating an attenuation correction technique utilising aligned Magnetic Resonance Imaging (MRI) of the thorax. This permits threedimensional quantitative analysis of intra-pulmonary deposition by a variety of techniques performed on a RISC workstation. Deposition of nebulised radio-aerosols (99mTc labelled human serum albumin) of 1.5μm MMAD (Optimist, Medic-Aid) and 6.5μm MMAD (Inspiran Bard) has been now been assessed in 12 subjects. All subjects were non-smokers and with no evidence of small airways disease. The aerosols were inhaled at tidal volume in a controlled manner in the erect, seated position. Using a shell analysis (Conway and Holgate 1994) the pattern of deposition for the total mass per shell and for surface density per shell was assessed. SPECT and MRI were found to be more sensitive than planar scint...

Radiologic Findings of Adult Primary Immunodeficiency Disorders: Contribution of CT

We wished to review the chest radiographic and computed tomographic (CT) findings in adults with primary immunodeficiency disorders, and to evaluate the influence of CT on the treatment of these patients. Retrospective blinded review of radiographs, CT scans, and clinical data. National referral center for immunodeficiency disorders. Forty-six chest radiographs and 22 CT examinations of subjects with primary immunodeficiency disorders were independently scored. Nineteen of the subjects who had CT scans had B-cell deficiency, while 3 had T-cell deficiency. CT-detected bronchiectasis in 15 of 19 subjects with B-cell deficiency, compared with 7 cases detected on chest radiograph. Unsuspected upper lobe bronchiectasis was found on CT in 15 cases. Other CT findings in this group included small nodules in seven subjects, interstitial lines in four, air trapping in seven, ground glass or parenchymal consolidation in nine, evidence of small airways disease in nine, and mucus plugs in four. Two of the three subjects with T-cell disorders showed cavitation and two had unsuspected reactive mediastinal adenopathy. Clinical management appeared to be altered in five subjects with B-cell deficiency by CT findings of severe focal or diffuse bronchiectasis or small airways disease. Additionally, CT localized the bleeding site in three subjects with hemoptysis. CT is valuable for detection of bronchiectasis in subjects with B-cell immunodeficiency and may alter treatment of these patients.

Role of Cardiorespiratory Abnormalities, Smoking and Dive Characteristics in the Manifestations of Neurological Decompression Illness

1. Blind analysis of contrast echocardiograms to detect intracardiac shunts, blind analysis of lung function tests for evidence of small airways disease, smoking history and dive characteristics were examined in an attempt to explain neurological symptoms that occurred within 5 min of surfacing from unprovocative dives. 2. Pulmonary abnormalities were significantly more frequent in those divers without intracardiac shunts (50%) than in those with shunts (0%). Smoking was more common in those divers without shunts (55% versus 15%), although this just failed to reach conventional significance levels. Divers without shunts experienced cerebral rather than spinal symptoms after significantly shallower dives with lower tissue nitrogen loads. Depths of dives, tissue nitrogen loads and clinical manifestations in those divers without shunts were similar to the findings in divers who had symptoms after rapid ascents. Despite conservative dive profiles, clinical manifestations in divers with shunts resembled those observed after missed decompression stops. 3. The findings suggest that occult lung disease, and probably smoking, increase the risk of neurological symptoms, even after unprovocative dives, and the similarity of the dive profiles and clinical manifestations to cases with rapid ascents suggest that pulmonary barotrauma and arterial gas embolism are responsible. In divers with intracardiac shunts the different dive profiles and clinical manifestations imply that there is another mechanism, involving different tissue and bubble nitrogen kinetics resulting in venous gas liberation and peripheral amplification in embolized tissues, rather than paradoxical embolism per se.

Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT.

The purpose of this study was to evaluate the significance of bronchial dilatation identified on high-resolution CT scans obtained after heart-lung transplantation. Bronchial dilatation has been identified on pathologic specimens and on high-resolution CT scans of patients with severe bronchiolitis obliterans after lung transplantation, but this finding has not previously been systematically studied as a manifestation of this complication. We studied the high-resolution CT scans of 16 patients who had had heart and lung transplantation at least 1 year before, and compared the percentage of dilated bronchi with evidence of small airways disease shown on pulmonary function tests. We found a close correlation between the percentage of bronchi in the lower lobes that were dilated and the percent predicted forced expiratory volume in 1 sec, forced vital capacity, and forced expiratory flow between 25% and 75% of vital capacity. No other feature identified on high-resolution CT scans correlated with pulmonary function abnormalities. We conclude that dilatation of the lower lobe bronchi is a good indicator of bronchiolitis obliterans in this population, and that the percentage of dilated bronchi generally increases with increasing pulmonary dysfunction.

Exercise-induced pulmonary hemorrhage

Exercise-induced pulmonary hemorrhage (EIPH) is characterizedby the presence of blood in the tracheobronchial airways after exercise. Most breeds used for strenuous exercise are affected. The prevalence of EIPH, irrespective of geographical location, has been reported to vary from 30% in Standardbred racehorses to 70% in Thoroughbred horses used for racing, jumping, eventing, steeplechase and polo. In addition to endoscopic confirmation, pulmonary hemorrhage can be recognized by identification of hemosiderophages (macrophages containing intracytoplasmic hemosiderin) in aspirates of tracheobronchial secretions. Detailed examinations of lungs from horses with a confirmed history of EIPH have identified certain consistent morphologic features that provide strong circumstantial evidence for bronchial arterial bleeding. Evidence of pulmonary hemorrhage is characteristically seen in the dorsocaudal regions of the caudal lung lobes. Stained a light brown-bronze color these regions are symmetrically distributed and in the inflated lung have a fine reticular pattern. The subpleural bronchial arteries are more prominent and appear enlarged and more tortuous in stained regions of the lung. Subgross examination of transverse slices of the caudal lung suggest that the hemorrhage occurs primarily in the dorsal bronchopulmonary segments with the dorsobasal bronchopulmonary segment being most severely involved. Affected regions have gross evidence of small airway disease with increased bronchial arterial supply around these airways and within the parenchyma. On microscopy, affected parenchymal regions have extensive interstitial fibrosis. Large accumulations of hemosiderophages are located within airspaces, terminal airways and within the increased connective tissue around airspaces and airways. Microangiographs of lung sections perfused with latex and barium sulfate revealed marked proliferation of the bronchial arterial circulation in lung regions with evidence of pulmonary hemorrhage. The expanded vascular network appeared to be focused on diseased small airways.

Clinical manifestations and consequences of influenza

The spread of influenza virus through a community typically causes large increases in medical visits for febrile respiratory disease. Increased school absenteeism occurs early in the epidemic, and school children appear to be important for disseminating the virus. Industrial absenteeism, hospitalizations of adults and infants for pneumonia, and deaths due to pneumonia-influenza all tend to peak later in the epidemic. Although influenza infection rates are highest in persons of school age, hospitalizations and deaths occur primarily in infants and in the elderly, particularly among those with pulmonary, cardiovascular, or other debilitating disorders. Influenza viruses can be spread by aerosol or contact. The primary target cells are those of the respiratory epithellum. In healthy adults, the typical influenza syndrome includes fever, cough, and general aches for three to seven days, but lassitude, cough, and evidence of small-airways disease may persist for weeks. Laryngotracheobronchitis, pneumonia, and unexplained fever are prominent manifestations of influenza that lead to hospitalization of young children. Adults are more likely to have complications of bacterial pneumonia and worsening of chronic pulmonary disease or congestive heart failure. Less frequent complications include myositis, various neurologic disorders, and Reye's syndrome. These consequences of influenza clearly justify strenuous efforts at prevention and control.

Long term pulmonary consequences of oesophageal atresia with tracheo-oesophageal fistula.

Lung function was studied in 20 children, aged 8-17 years, who had successfully repaired oesophageal atresia with tracheo-oesophageal fistula. Spirometry and plethysmography showed mild restrictive lung disease. Airways obstruction was assessed using maximal expiratory and inspiratory flow-volume loops in air and after breathing a helium-oxygen mixture. Analysis of the flow-volume data demonstrated significant obstruction at the level of the trachea and little evidence of small airways disease. Bronchial hyperreactivity, as assessed by histamine challenge, was present in 22% of subjects. Respiratory and oesophageal symptoms were common, but decreased in frequency with increasing age. The mechanisms involved in the frequent respiratory symptoms these children suffer are discussed in the light of the physiological findings.

Respiratory complications of relapsing polychondritis.

<b>Gibson, G. J. and Davis, P. (1974).</b><i>Thorax</i>, <b>29</b>, 726-731. <b>Respiratory complications of relapsing polychondritis.</b> The respiratory function of a patient with relapsing polychondritis is described. He had severe airflow obstruction due to disease of both the extra and intrathoracic large airways. Evidence of small airways disease was lacking. The airflow obstruction was probably due to a combination of structural narrowing and an enhanced dynamic effect. Despite the severity of his disease the patient9s exercise capacity was only slightly reduced but he developed carbon dioxide retention on exercise. Involvement of the airways is a common feature of this rare disease and demands full physiological and radiographic assessment if tracheostomy or other surgical procedure is contemplated.