Introduction

Idiopathic pulmonary fibrosis (IPF) is one of the morecommonly occurring interstitial lung diseases [1, 2]. Pa-tients with IPF are at risk for a variety of acute pulmo-nary complications, including infection, pulmonary em-bolism, and pneumothorax [2, 3, 4, 5]. Over the past2 years we have observed spontaneous extra-alveolarair collections in several patients with IPF. Early detec-tion of extra-alveolar air collections in order to preventadditional morbidity or potential life-threatening com-plications is a frequent charge of both the clinician andthe radiologist. Although some patients with sponta-neous extra-alveolar air collection are asymptomatic,clinical findings include chest pain, cough, and dyspnea.In specific clinical situations, recognition and determi-nation of extra-alveolar air distribution and severity iscrucial for adequate patient management.

To our knowledge, despite that CT is commonly usedto assess infiltrative lung diseases, there has been limit-ed information available in the radiological literatureabout the frequency, mode of presentation, and imagingfindings of these IPF-related complications [5]. The aimof the present study was to describe the chest radio-graphic and CT findings of extra-alveolar air collectionsin 9 patients with IPF and to determine its frequency inidiopathic pulmonary fibrosis.

Materials and methods

Between January 1994 and July 1997, 78 consecutive pa-tients with histologically proven or clinically diagnosedIPF were seen at our hospital. A retrospective reviewof the radiological and clinical records yielded 9 patients(11.5 %) with extra-alveolar air collections demonstrat-ed at CT. The patients included six women and threemen who had a mean age of 65 years (range26±90 years). None of these patients had been intubatedor biopsied close to the time of detection of extra-alveo-lar air. Four patients did not smoke, and 5 patients had

Eur. Radiol. 10, 108±113 (2000) Ó Springer-Verlag 2000

Chest radiology EuropeanRadiology

Original article

Spontaneous pneumothorax and pneumomediastinum in IPFT. Franquet1, A. GimØnez1, S. Torrubia1, J.M. SabatØ1, J.M. Rodriguez-Arias2

1 Department of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona, San Antonio Ma Claret 167,E-08025 Barcelona, Spain

2 Department of Respiratory Medicine, Hospital de Sant Pau, Universidad Autonoma de Barcelona, San Antonio Ma Claret 167,E-08025 Barcelona, Spain

Received: 9 October 1998; Revised: 26 January 1999; Accepted: 6 April 1999

Abstract. Patients with idiopathic pulmonary fibrosis(IPF) are at risk for a variety of acute pulmonarycomplications, including pneumothorax and pneumo-mediastinum. Our aim was to describe the radio-graphic and CT findings and to determine the fre-quency of complicating spontaneous pneumothoraxand pneumomediastinum in patients with IPF. A ret-rospective study was performed including 78 consec-utive patients who underwent CT scanning of thechest and who had confirmed IPF. The chest radio-graphs and CT scans were reviewed by two chest radi-ologists and classified as showing features of extra-al-veolar air collections. The CT scans showed extra-al-veolar air in 9 (11.2 %) of 78 patients (six femalesand three males; age range 26±90 years, mean age65 years). Pneumothorax was demonstrated in 5 pa-tients and mediastinal air collections in 4 patients.All patients had dyspnea for 1±48 months (mean14 months). Of the five cases with pneumothorax,four developed acute onset of dyspnea and pleuriticchest pain, whereas 1 patient had a relatively stablefunctional status. Of the 4 patients with pneumome-diastinum, three presented with nonpleuritic chestpain and acute dyspnea. Chest radiographs showedextra-alveolar air in 6 patients. Three cases were pre-dicted to be negative by chest radiographs. Follow-upCT showed that air collections had resolved com-pletely in 5 patients. Two patients died of respiratoryfailure within 4 months after CT. Extra-alveolar airshould be recognized as a relatively common IPF-re-lated complication. Chest CT is a useful imagingmethod in determining air collections in patientswith IPF that become acutely breathless and theirchest radiograph fails to reveal the presence of ex-tra-alveolar air.

Key words: Idiopathic pulmonary fibrosis ± Pneu-mothorax ± Pneumomediastinum ± CT

Correspondence to: T. Franquet

smoking histories of more than 40 pack-years. The clini-cal histories were reviewed to identify any underlyingmedical condition or potential causes of extra-alveolarair. None of the patients had underlying connective tis-sue disorder or other causes of pulmonary fibrosis.Chest radiographs and CT scans were reviewed in all pa-tients and were analyzed by two chest radiologists (T.F.and A. G.) with regard to patterns and distribution ofpulmonary abnormalities and abnormal air collections.The conclusion was reached by consensus.

All patients had thin-section CT performed as a partof a systematic evaluation in patients with infiltrativelung diseases. The CT scans were performed with oneof two scanners (Toshiba 900 TCT, Toshiba Medical Sys-tems, Tokyo, Japan; or Somaton Plus 4, Siemens, Erlan-gen, Germany). The CT scans were obtained at the sus-pended end-inspiratory volume with imaging time of 1or 2 s. Thin-collimation (1 or 2 mm) continuous sectionswere obtained from lung apices to below the costo-phrenic angles, at 10-mm intervals, 120 kV and240 mA. A 350-mm field of view and a 512 � 512 recon-struction matrix were used. Images were reconstructedwith a high-spatial algorithm for parenchymal analysisand re-imaged with a standard algorithm for mediastinalevaluation. No intravenous contrast material was used.Patients were scanned in the supine position, with addi-tional scans obtained in the prone position, when neces-sary, to demonstrate the reversibility of dependent areasof attenuation. All CT scans were reviewed on the hardcopy with two windows settings: one for mediastinalsoft tissues (window level 35 HU, window width 350HU) and one for the lung parenchyma (window level±700 HU, window width 1600 HU).

The CT scans were assessed for the presence and dis-tribution of the following parenchymal abnormalities:interlobular septal thickening, distortion of structuralfeatures, ground-glass attenuation, traction bron-chiectasis and honeycombing. Parenchymal abnormali-ties were also assessed with regard to laterality of in-volvement; focal, patchy, or diffuse distribution; pre-dominantly central or peripheral localization; and up-per, middle, or lower zonal predominance. Mediastinalair was assessed with regard to its location within themediastinum: anterior, middle, and posterior compart-ments as well as for a specific air dissection of the viscer-al sheats (esophago-tracheal sheats, peribronchio-vas-cular sheats, and perivascular sheats of the cephaladvessels). Follow-up CT scans were also available in allnine cases. The follow-up period ranged from 1 to8 months (mean 4 months).

Results

Clinical findings and clinical course

From the 78 patients, 35 were diagnosed on the basis oftransbronchial lung biopsy (n = 20), open-lung biopsy(n = 13), or autopsy (n = 2). The remaining 43 patientshad clinical, functional, and radiographic criteria of IPF[6]. All patients had dyspnea for 1±48 months (mean

14 months). Of the five cases with pneumothorax, fourdeveloped acute onset of dyspnea and pleuritic chestpain, whereas 1 patient had a relatively stable functionalstatus (Fig. 1). Two patients required no treatment be-cause no progression of pneumothorax was seen; 1 pa-tient was successfully treated with tube thoracostomy,whereas the other required thoracoscopic talc poudragefor persistent air leak. Of the 4 patients with pneumo-mediastinum, three presented with nonpleuritic chestpain and acute dyspnea. Overall, the average onset ofacute dyspnea and/or chest pain was 4 h (range 1±8 h).In symptomatic patients, the interval between acute on-set of symptoms and radiographic documentation rang-ed from 2 to 12 h (median interval 3 h). Two patientsdied of respiratory failure within 4 months after CT.

Radiographic and CT findings

Computed tomography was the gold standard in defin-ing the presence of extra-alveolar air. A total of 9(11.2 %) of the 78 patients studied had extra-alveolarair visible on CT scans; of these, five demonstrated CTfindings consistent with pneumothorax, and four dem-onstrated features of pneumomediastinum. All 9 pa-tients had abnormal findings on admission chest radio-

T.Franquet et al.: Spontaneous pneumothorax and pneumomediastinum in idiopathic pulmonary fibrosis 109

b

1a

Fig.1a,b. A 26-year-old woman with familial pulmonary fibrosiswho presented with exacerbated cough and dyspnea. a Posteroan-terior chest radiograph demonstrates bilateral diffuse coarse, irreg-ular, and linear opacities. Extra-alveolar air was not visible. b ACT scan (2-mm collimation, high-spatial-frequency reconstructionalgorithm) through the upper lobes demonstrates multiple 1-cm di-ameter subpleural cysts and a left loculated small pneumothorax(arrow)

graphs compatible with infiltrative lung disease. Thepredominant radiographic findings were bilateral, dif-fuse reticular (n = 6) or reticulonodular pattern (n = 2))and air±space areas of opacity (n = 2), with the middle(n = 7) and lower (n = 7) lung zones more frequently in-volved than the upper (n = 2) lung zone. In six of thesepatients, the parenchymal abnormalities were thoughtto represent honeycombing. Chest radiographs showedextra-alveolar air in 6 patients (7.6 %), pneumothorax(n = 4), and pneumomediastinum (n = 2; Fig. 2). Onepatient had experienced multiple episodes of pneu-mothorax. Three cases were predicted to be negativeby chest radiographs.

The most common findings on thin-section CT scanswere a diffuse (n = 6) or patchy (n = 3), bilateral, reticu-lar pattern which was present alone (n = 5) or mixed

with ground-glass opacities (n = 4). Bilateral patchy(n = 2) or diffuse (n = 4) areas of honeycombing werepresent in 6 patients. Overall, parenchymal abnormali-ties showed a subpleural predominance.

By CT, extra-alveolar air was demonstrated in 9(11.2 %) of 78 patients. Pneumothorax was seen in 5 pa-tients and pneumomediastinum in 4 patients. Pneumo-thoraces were unilateral in all five cases (right, 3; left,two; Fig. 3). The right pneumothoraces were extensivein all 3 patients, whereas in the left side, pneumothoraxappeared loculated in the apical and lower zones, re-spectively. Among the patients with pneumomediasti-num, the air was noted in the anterior compartment in3 patients (retrosternal space, n = 3; pretracheal space,n = 2), in the middle compartment in 4 patients (per-iesophageal space, n = 4; left paratracheal space, n = 4),and in the posterior compartment in 1 patient (peri-aor-tic and perivertebral spaces). Air in the peribronchialsheats (interstitial emphysema) was noted in 3 cases(Figs. 4, 5).

At follow-up CT, in the 4 patients whose initial chestradiographs or CT showed pneumomediastinum, aircollections resolved completely within 2 months. TheCT findings in 2 patients with loculated pneumothorac-es remained unchanged for 5 months. Pneumothoraxwas completely resolved in 3 cases. Two patients died

T. Franquet et al.: Spontaneous pneumothorax and pneumomediastinum in idiopathic pulmonary fibrosis110

Fig 2a±c. A 70-year-old woman with acute onset of dyspnea andchest pain. a Collimated frontal chest radiograph of the left upperpart of the chest demonstrates thin band of gas (arrows) outliningleft main bronchus and middle esophagus. b A CT scan (2-mm col-limation, high-spatial-frequency reconstruction algorithm) demon-strates gas around the esophagus (arrowheads). c A CT scanthrough the upper lobes demonstrates gas into the peribronchovas-cular bundle (interstitial emphysema) outlining left main bronchus(arrow) and descending aorta

a

b

c

of respiratory failure within 4 months after CT. A sum-mary of the radiographic and clinical data of patients ispresented in Table 1.

Discussion

Idiopathic pulmonary fibrosis has a poor prognosis, with50% of patients dying 5 years after the onset of symptoms[6]. Caring for patients with IPF is a challenge, becausetherapy may not be especially helpful and the illness usu-ally progresses. Several specific complications have beendescribed in patients with IPF, including respiratory fail-ure (39 %), heart failure (14 %), and bronchogenic carci-noma (10 %) [3]. However, the issue of spontaneous ex-tra-alveolar air in patients with IPF has received limitedattention in the radiology literature [2, 3, 4, 5].

Despite limited accuracy, chest radiograph is still themost widely used diagnostic modality for IPF-relatedcomplications. In a study of 95 patients with IPFMcCloud et al. [2] found pneumothorax on chest radio-graph in 7.4 % of cases. Similarly, Picado et al. [4] foundspontaneous pneumothorax in 3 (3.6 %) of 82 patientswith IPF. In our study extra-alveolar air was identifiedin 6 (7.6 %) patients, which was similar to the incidencereported by McCloud et al. [2].

To date, CT has proved to be of great value in the as-sessment of infiltrative lung disorders. However, despitethese advantages, the usefulness of CT in the detectionof spontaneous extra-alveolar air collections in IPF hasbeen limited [5].

In terms of the analysis of extra-alveolar air in pul-monary fibrosis, we considered CT as the diagnostic ref-erence standard. Our results, obtained from a series of78 patients with IPF, confirmed that spontaneous extra-alveolar air is a relatively common related complicationof IPF that occurred in 11.5% of our cases. The com-plexity of parenchymal abnormalities in such patientsmakes identification of extra-alveolar air difficult. Onchest radiographs, air collections were identified in 6 pa-tients (7.6 %), pneumothorax was noted in 4 (5.1 %),and pneumomediastinum in 2 patients (2.5 %). In com-parison with chest radiographs, CT scans provide moreprecise information about the presence, extent, and dis-tribution of the extra-alveolar air. In addition, the prev-alence of this complication likely increases when newmethods, such as CT, come into general use for the eval-uation of these patients.

The clinical manifestations of spontaneous extra-al-veolar air in IPF are varied and range from roentgeno-graphic findings alone in asymptomatic patients to se-vere respiratory insufficiency. Symptoms include dys-pnea, cough, and chest pain. In a recent review of 5 pa-tients with pneumomediastinum and IPF, all patientspresented with moderate to severe cough at the time ofCT scan, and 4 patients died subsequently of respiratoryfailure 1 week to 6 months after CT [5]. In this series, all9 patients presented with severe dyspnea at the time ofCT examination, whereas acute chest pain was the pre-senting clinical complaint in 7 patients and 2 patientspresented with cough.

It has been suggested that rupture of alveoli second-ary to an increased intrathoracic pressure plays a signif-icant role in the development of pneumomediastinumallowing air to enter the interstitial space dissectingalong peribronchial sheats and extending into the medi-astinum [7, 8, 9, 10]. It is well known that this process isdifficult, if not impossible, to detect by chest radiographon a background of complex parenchymal abnormali-ties. Air in the peribronchial sheats (interstitial emphy-sema) can be associated with impairment of respiratory

T.Franquet et al.: Spontaneous pneumothorax and pneumomediastinum in idiopathic pulmonary fibrosis 111

a b

Fig.3a,b. A 67-year-old woman who presented with acute dyspneaand chest pain. a Posteroanterior chest radiograph shows bilateraldiffuse reticular opacities with upper lobe predominance. In thelower left hemithorax a loculated air collection is also identified(arrows). b A CT scan (2-mm collimation, high-spatial-frequencyreconstruction algorithm) confirmed an ovoid loculated pneu-mothorax

function and/or chest pain, possibly resulting from com-pression of small vessels by the interstitial air [10]. It wasclinically significant that 3 of the 4 patients with pneu-momediastinum and chest pain had interstitial emphy-sema visible on CT scans.

Although extra-alveolar air has not been recognizedas a fatal complication in IPF, an early diagnosis andtreatment are crucial because that may result in a de-creased morbidity rate. The partial adherence of thelung to the chest wall, due to inflammation, may insti-gate an unusual configuration and/or loculation of thepleural air collections. In this study, loculated pneumo-thoraces were seen in 2 patients. It is well known thatin pulmonary fibrosis pneumothorax usually does notrespond easily to tube thoracostomy due to the highnegative pressure required for lung reexpansion [3]. In-dications for pneumothorax drainage include collec-tions estimated to exceed 25 % of the volume of onehemithorax, an enlarging pneumothorax indicating per-sistent air leak, or any size pneumothorax that causesdyspnea or severe chest pain [11, 12]. Nevertheless, tho-racoscopic talc poudrage, thoracostomy tube withchemical pleurodesis, and pleurectomy are proceduresusually reserved for severely symptomatic patients withrecurrent pneumothorax or persistent bronchopleuralfistula. In our study group, only 1 of the 5 patients withpneumothorax required thoracoscopic talc poudrage.By contrast, spontaneous pneumothorax resolution wasnoted in 2 cases.

In summary, extra-alveolar air should be recognizedas a relatively common IPF-related complication. Inthe appropriate clinical setting, namely a patient withIPF and an acute onset of dyspnea and/or chest pain,we believe that CT is a very helpful and cost-effectiveexamination for evaluating patients suspected of havingextra-alveolar air collections. Computed tomography isalso valuable in determining air collections in patientswith IPF that become acutely breathless and their chestradiograph fails to reveal the presence of extra-alveolarair. Additional benefits obtained from the CT examina-tion include alternative diagnoses and ease of compari-son of CT examinations in time.

T. Franquet et al.: Spontaneous pneumothorax and pneumomediastinum in idiopathic pulmonary fibrosis112

Fig.4a,b. A 70-year-old woman with acute chest pain and exacer-bation of dyspnea. a Posteroanterior chest radiograph shows a bi-lateral diffuse reticular pattern and significant loss of lung volume.Extensive pneumomediastinum is present. Note gas outlining mainbronchi (arrows), aortic arch, and the wall of an incidental hiatalhernia. b On lateral radiograph mediastinal air outlines extrapleu-ral tissues of anterior chest wall, pulmonary artery, and ascendingaorta

a b

Fig.5. A 45-year-old man with idiopathic pulmonary fibrosis andacute onset of dyspnea and chest pain. A CT scan (1-mm collima-tion, high-spatial-frequency reconstruction algorithm) reveals bi-lateral fine reticular opacities peripherally distributed. These find-ings were better demonstrated in the lung bases (not shown).Note a small amount of interstitial air surrounding the left bronchi-al tree (arrow)

References

1. Müller NL, Staples CA, Miller RR, Vedal S, Thurlbeck WM,OstrowDN (1987) Disease activity in idiopathic pulmonary fi-brosis: CT and pathologic correlation. Radiology 165: 731±734

2. McCloud TC, Carrington CB, Gaensler EA (1983) Diffuse in-filtrative lung disease: a new scheme for description. Radiology149: 353±363

3. Panos RJ, Mortenson R, Niccoli SA, King TE Jr (1990) Clinicaldeterioration in patients with idiopathic pulmonary fibrosis.Causes and assessment. Am J Med 88: 396±404

4. Picado C, Gomez de Almeida R, Xaubet A et al. (1985) Spon-taneous pneumothorax in cryptogenic fibrosing alveolitis. Res-piration 48: 77±80

5. Fujiwara T (1993) Pneumomediastinum in pulmonary fibrosis.Detection by computed tomography Chest 104: 44±46

6. Turner-Warwick M, Burrows B, Johnson A (1980) Cryptogenicfibrosing alveolitis: clinical features and their influence on sur-vival. Thorax 35: 171±180

7. Gray JM, Hanson GC (1966) Mediastinal emphysema: aetiolo-gy, diagnosis, and treatment. Thorax 21: 325±332

8. Bejvan SM, Godwin JD (1996) Pneumomediastinum: old signsand new signs. AJR 166: 1041±1048

9. Abolnik I, Lossos IS, Breuer R (1991) Spontaneous pneumo-mediastinum. A report of 25 cases. Chest 100: 93±95

10. Macklin CC (1939) Transport of air along sheats of pulmonicblood vessels from alveoli to mediastinum. Arch Intern Med64: 913±926

11. Conces DJ Jr, Tarver RD, Gray WC, Pearcy EA (1988) Treat-ment of pneumothoraces utilizing small caliber chest tubes.Chest 94: 55±58

12. Klein JS, Schultz S, Heffner JE (1995) Interventional radiologyof the chest: image-guided percutaneous drainage of pleural ef-fusions, lung abscess, and pneumothorax. AJR 164: 581±588

T.Franquet et al.: Spontaneous pneumothorax and pneumomediastinum in idiopathic pulmonary fibrosis 113

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